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Biomaterials

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Multifunctional nanostructures for diagnostic and therapeutic of diseases

Although much progress has been made intreatment of diseases and cancer this last decade, new approaches are necessary at the same time for improving existing therapies or developing new techniques of treatment in order to minimise deleterious side effects and to increase the patient survival rates. The fast growing research in nanoscale science and nanotechnology has brought many potential opportunities as well aschallenges in innovations in medicine. .

The symposium will focus on state-of-the-art on multifunctional nanomaterials designed for revolutionizing the field of diagnosis and therapy. The recent advances in new materials, advanced characterizations, and breakthrough innovationsfor therapy and early diagnosis will provide a strong basis for the symposium.

Scope:

There is currently a medical need to develop novel efficient nano-objects for treatment of diseases. Image-guided therapy will be also crucial for the development of these compounds. Therefore the future of nanomedicine lays in the development of multifunctional nanoplatforms which combine both therapeutic components and multimodality imaging and which also act locally in tumors to avoid side-effects.

The explosive growth of nanotechnology has brought challenging innovations in the synthesis of multifunctional nano-objects for medicine, able to revolutionize the field of diagnosis and therapy. Furthermore, one important input of today’s nanotechnology in biology is that their design will also allow real progress to achieve temporal and spatial site local therapy and imaging. Such a breakthrough is made possible by the development of multifunctional biocompatible nanosystems resulting from cutting-edge researches based on multi-disciplinary approaches.

This symposium will be a good opportunity to bring together researchers from different communities (organic chemistry, nanoparticles synthesis, material sciences, biology, physics, engineering and medicine) and exchange the latest developments in the synthesis and funtionnalisation of multifunctional bioactive nano-objects, as well as their biomedical applications.

Publication:

Articles should be submitted via the online system at: https://mc.manuscriptcentral.com/rsfs together with a cover letter mentioning that the paper is for consideration for inclusion in the issue 'Multifunctional nanostructures for diagnosis and therapy of diseases'. The deadline is 10th of June.

Hot topics to be covered by the symposium

  • Design, synthesis and characterization of nanoparticles: inorganic, polymers, liposomes, dendrimers...
  • Biofunctionalisation of nanoparticles
  • Targeting strategies
  • Drug delivery systems
  • Biomedical Imaging (e.g. MRI, MPI, SPECT, PET)
  • Therapeutics (e.g, hyperthermia, curie theraphy)
  • Diagnostics  (e.g., enzymatic assay, immunoassay, biosensing)
  • Biodistribution/bioelimination
  • Nanotoxicology

List of keynote speakers (to be updated):

  • Mary McCommack, University College London Hospitals, UK.
  • O. Tillement, Université Claude Bernard-Lyon, France
  • Stefaan Soenen,  University of Leuven, Belgium.
  • Steve Colan, College of Medicine, Swansea University, UK.
  • Delphine Felder-Flesch, IPCMS, France.
  • Michael Farle, Duisburg – Essen University, Germany.
  • Michael Giersig, Freie Universität Berlin, Germany.
  • Alessandro Lascialfari, Univ. of Milano, Italy.
  • Kerry Chester, UCL Cancer Institute, University College London.UK
  • Florence Gazeau, Université Paris-Diderot, France
  • Theresa Pellegrino

List of  invited speakers (to be updated):

  • Lanry Yung, National University of Singapore. Singapore
  • Lim Jit Kang, Universiti Sains Malaysia, Malaysia
  • Daniel Ortega, Ciudad Universitaria de Cantoblanco, Spain
  • Olivier Sandre, Université de Bordeaux,France
  • Paulo Morais, University of Brasilia, Brasilia
  • Alexandro Lappas,Foundation for Research and Technology – Hellas, Greece
  • Marie-Hélène Delville, ICMCB, Bordeaux, France
  • Etelka Tombascz, University of Szeged, Hungary
  • Sara Staniland, University of Sheffield, UK.
  • Jianping Xie, National University of Singapore. Singapore
  • Tapas Sen,University of Central Lancaster, UK.
  • Shinya Maenosono, Japan Advanced Institute of Science and Technology, Japan
  • Jesus de la Fuente, University of Zaragoza, Spain
  • J.O. Durand, Univ de Montpellier, France
  • Xu Chenjie, NTU, Singapore.
  • Laurence Motte, Univ Paris XIII, France
  • Fabrizio Mancin, Univ. of Padova, Italy
  • Stephane Mornet, Université de Bordeaux, France
  • F. Ratto, CNR-IFAC, Italy
  • Tatiana Da Ros, University of Trieste, Italy

Scientific Committee:

  • Simon Spassov, Centre de Physique du Globe de l'Institut Royal Météorologique de Belgique, Belgium
  • Claire Billotey, Hospices civil de Lyon, France
  • Damien Mertz, IPCMS, Strasbourg, France
  • Puerto Morales, Instituto de Ciencia de Materiales de Madrid, Spain
  • Sophie Laurent, University of Mons, Belgique
  • Daniel Ortega, Ciudad Universitaria de Cantoblanco, Spain
  • Zulmira Lacava, Univ. of Brasilia, Brazil
  • Plazaola Fernando, Univ Basque Country, Leioa, Spain
  • Claudia Innocenti, Univ. of Florence, Italy 
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Strategy for diagnosis and therapy : C. Sangregorio - A. Lascialfari
13:30
Authors : J.M. DE LA FUENTE*
Affiliations : Instituto de Ciencia de Materiales de Aragón, CSIC-Universidad de Zaragoza, Spain. & Shanghai Jiao Tong University, P.R. China. *jmfuente@unizar.es

Resume : In the last decades, inorganic nanoparticles have been steadily gaining more attention from scientists from a wide variety of fields such as material science, engineering, physics or chemistry.The very different properties compared to that of the respective bulk, and thus intriguing characteristics of materials in the nanometre scale, have driven nanoscience to be the centre of many basic and applied research topics. Moreover, a wide variety of recently developed methodologies for their surface functionalization provide these materials with very specific properties such as drug delivery and circulating cancer biomarkers detection. In this talk we describe the synthesis and functionalization of magnetic and gold nanoparticles as therapeutic and diagnosis tools against cancer. Gold nanoprisms (NPRs) have been functionalized with PEG, glucose, cell penetrating peptides, antibodies and/or fluorescent dyes, aiming to enhance NPRs stability, cellular uptake and imaging capabilities, respectively.3,4 Cellular uptake and impact was assayed by a multiparametric investigation on the impact of surface modified NPRs on mice and human primary and transform cell lines. Under NIR illumination, these nanoprobes can cause apoptosis. Moreover, these nanoparticles have also been used for optoacoustic imaging,5 as well as for tumoral marker detection using a novel type of thermal ELISA nanobiosensor using a thermosensitive support.6 References [1] J. Conde, A. Ambrosone, V. Sanz, Y. Hernandez, F. Tian, P. V. Baptista, M. R. Ibarra, C. Tortiglione, J. M. de la Fuente, ACS Nano 6, 8316(2012) [2] J. Conde, F. Tian, Y. Hernández, C. Bao, D. Cui, M. R. Ibarra, P. V. Baptista, J. M. de la Fuente. Biomaterials 34, 7744 (2013) [3] B. Pelaz, V. Grazú, A. Ibarra, C. Magén, P. del Pino, J. M. de la Fuente. Langmuir 28, 8965 (2012). [4] M. Pérez-Hernández, P. del Pino, S.G. Mitchell, M. Moros, G. Stepien, B. Pelaz, W.J. Parak, E. M. Gálvez, J. Pardo, J. M. de la Fuente. ACS Nano9, 52 (2015). [5] C. Bao, N. Beziere, P. del Pino, B. Pelaz, G. Estrada, F. Tian, V. Ntziachristos, J. M. de la Fuente, D. Cui. Small9, 68 (2013). [6] E. Polo, P. del Pino, B. Pelaz, V. Grazu, J.M. de la Fuente. Chemical Communications 49, 3676 (2013).

R.01.2
13:50
Authors : J. Volatron(1),* F. Carn(1), M. Hemadi(2), Y. Javed(3), D. Alloyeau(3), F. Gazeau(1)
Affiliations : (1) Laboratoire Matière et Systèmes Complexes, 10 rue Alice Domon et Léonie Duquet, 75205 Paris cedex 13 (2) Laboratoire ITODYS, UMR 7086, Université Paris Diderot, 15 rue J.A. de Baïf, 75205 Paris cedex 13 (3) Laboratoire Matériaux et Phénomènes Quantiques, 10 rue Alice Domon et Léonie Duquet, 75205 Paris cedex 13

Resume : The use of inorganic nanoparticles in the field of the nanomedecine is rapidly expanding allowing news treatments for various diseases. Thanks to their size, optical or magnetic properties and functionalization, metal oxide nanoparticles are widely used for their significant potential in theranostics. Although the potential toxicity of such nanomaterials is extensively studied, their long term fate, their degradation and the evolution of their properties in the organism are still poorly understood. Here we propose a multi-scale approach to study the life cycle of metal oxide nanoparticles in biological environments based on the evolution of their physical and morphological properties. Our group has previously shown that iron oxide nanoparticles injected intravenously in mice under-went local intracellular degradation within lysosomes of macrophages in spleen and liver (L. Lartigue, ACS Nano 7:3939-52 (2013), J. Kolosnjaj et al, ACS Nano, 9:7925-39 (2015)). The coexistence of iron rich ferritin protein in vicinity of degraded nanoparticles suggests the implication of these iron storage protein in the remediation of iron released by nanoparticles. In this work, we aim to decipher the degradation mechanism of iron oxide, cobalt iron oxide and gold-iron oxide nanohybrids and their processing by endogenous proteins such as apoferritin. We will present recent results concerning the degradation of maghemiteand cobalt ferrite NPs in a simple model of intracellular environment containing apoferritin proteins, which are the major intracellular iron storage proteins. We have studied the evolution of the NPs’ magnetic properties during degradation by Electronic Paramagnetic Resonance (EPR) and nuclear magnetic relaxation dispersion measurements (NMRD). In parallel the metal transfer to apoferritin and the evolution of NPs’ size, structure and colloidal state have been studied in solution by using liquid state high resolution transmission electronic microscopy, dynamic light scattering, small angle neutron scattering and UV-Vis spectroscopy. We will show that this original combination of complementary methods enables to shed light on the relation between the kinetics of nanoparticle degradation, the interactions of nanoparticles with proteins and the bioremediation of metal ions.

R..0
14:05
Authors : Gemma-Louise Davies
Affiliations : Department of Chemistry, University of Warwick

Resume : Magnetic resonance imaging (MRI) is a powerful non-invasive technique which becomes considerably more potent when contrast agents (CAs) are introduced. Superparamagnetic iron oxide nanoparticles have potential in biomedicine and have seen application as clinical MRI CAs, though their popularity has plummeted recently due to their low efficacy and patient safety concerns, including haemagglutination. There is therefore a real need for new CAs with excellent MRI contrast capabilities and good biocompatibility. In this work, an in situ procedure is used to prepare colloids of magnetite nanoparticles, exploiting the clinically approved anti-coagulant, heparin, as a templating stabiliser. These stable colloids demonstrate exceptionally strong MRI contrast capabilities, particularly at low fields (r1 values of 34.80 mM-1s-1 at 20 MHz and 88.43 mM-1s-1 at 0.01 MHz), which outperform the current clinical standards. Relaxometric investigations using nuclear magnetic resonance dispersion (NMRD) techniques demonstrate that this behaviour is due to interparticle interactions, thanks to the templating effect of heparin, resulting in strong magnetic anisotropic behaviour. The stable colloidal nanoparticles have also been shown to prevent protein-adsorption triggered thrombosis, which causes unexpected (and potentially fatal) problems in the clinic. These species therefore show strong potential for in vivo MRI diagnostics.

R.1.3
14:20
Authors : Benjamin P. Burke,a,b Hayley Bignell,a,b Tahani M. Al-Resheedi,a,b Alicja E. Kownacka,a Aristides Bakandritsos,c Christopher Cawthorneb,d and Stephen J. Archibalda,b*
Affiliations : a Department of Chemistry, University of Hull, Cottingham Road, Hull, HU6 7RX, UK; b Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, HU6 7RX, UK; c Department of Materials Science, University of Patras, 26504 Rio, Patras, Greece; d School of Biological, Biomedical and Environmental Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, UK.

Resume : The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities.1 The aim of this work is the development of silica coated iron oxide nanoparticles (NPs) radiolabelled with positron and gamma emitting isotopes to create agents which give signal in multiple imaging modalities with a potential therapeutic effect via magnetic hyperthermia. Super-paramagnetic iron oxide nanoparticles (SPIONs) are used in MRI to reduce the time taken for proton nuclei to transfer their spin to neighbouring proton nuclei, resulting in a loss of transverse magnetisation (T2 relaxation), causing a relative darkening in regions of SPION accumulation. Iron oxide nanoparticles (NPs) coated with siloxane PEG were optimised for core size and phase, hydrodynamic size, aqueous stability and magnetic properties. The NPs were radiolabelled using a direct chelator-free method2-3 with 68Ga and 99mTc for PET and SPECT respectively and their radiochemical stability assessed. In vivo imaging was carried out using µPET/CT, nanoSPECT/CT and a preclinical (11.7 T) MRI scanner to determine in vivo stability and assess biodistribution. Magnetic hyperthermia measurements have been carried out to determine the potential of therapeutic applications. 1. R. T. M. de Rosales, J. Labelled Compd. Radiopharm., 2014, 57, 298. 2. B. P. Burke et al., Faraday Discussions, 2014, 175, 59. 3. B. P. Burke et al., Nanoscale, 2015, 7, 14889.

R.01.3
14:35
Authors : Corinne Nardin
Affiliations : Université de Pau et des Pays de l'Adour - Institut des Sciences Analytiques et de Physico-chimie pour l'Environnement et les Matériaux - IPREM - Equipe de Physique et Chimie des Polymères - UMR 5254 PAU - (France)

Resume : To establish the mechanism of the functional self-assembly of DNA copolymers, we recently achieved the synthesis of either linear or comb/graft amphiphilic DNA copolymers. When composed of a poly(oxazoline) backbone and of hydrophilic short single stranded nucleic acid grafts, the resulting macromolecule undergoes self-assembly into vesicular structures in dilute aqueous solution. The surface activity of the DNA copolymer of higher hydrophilic weight fraction enabled the stabilization of an emulsion, which is sensitive to a biological stimulus when the nucleic acid grafts are aptamers that recognize specifically a protein. Structure formation through either self-assembly or nucleation polymerization into amyloid-like fibrils could also be fine-tuned by coupling a dipeptide to a nucleic acid sequence. Along this line, we recently evidenced that electrostatic interactions prevent amyloid beta (1-42) (Ab42) fibril formation and induces the disassembly of readily formed fibrils upon interaction with polyions of biological relevance, in particular short synthetic single stranded nucleotide sequences. Since the accumulation of misfolded Ab42 proteins is a key feature of Alzheimer’s disease, aggregation promotion or reduction at any stage of fibril genesis is of high relevance to advance the current understanding of the pathophysiology to identify in the future a cure against this disease that concerns an ever aging population.

R.01.4
14:50
Authors : Geoffrey Cotin, Christine Affolter-Zbaraszczuk, Catalina Bordeianu, Damien Mertz, Beatrice Uring-Lambert, Florent Meyer, D. Felder-Flesch, S. Begin-Colin
Affiliations : ?Institut de Physique et Chimie des Matériaux, UMR CNRS-UdS 7504 University of Strasbourg, 23 Rue du Loess, BP 43, 67034 Strasbourg, France ?INSERM, UMR 1121, 11 rue Humann, 67085 Strasbourg, France ?Nouvel Hôpital Civil, laboratoire d?Immunologie, 1 Place de l?hôpital, 67091 Strasbourg, France

Resume : In the field of the synthesis and functionalization of inorganic nanoparticles (NPs) for biomedical applications, most researches aim at developing multifunctional theranostic NPs which can both identify disease states and deliver therapy and allow thus following the effect of therapy by imaging. Iron oxide nanoparticles (NPs) are commercially used as T2 contrast agent for MRI and they are also currently developed for therapy by magnetic hyperthermia (MH). However one of the limitations of MH is the low heating power of usual magnetic nanoparticles (NPs), requiring a local injection of NPs in large quantities. Improving the properties in MH imply to improve the NPs magnetic properties which can be done by optimizing their magneto-crystalline anisotropy thus changing their morphology and/or composition. The tuning of the shape and of the composition by inducing magnetic exchange interaction in core-shell NPs consisting of a core with a high magnetic anisotropy and a shell with a small magnetic anisotropy (or the inverse) are promising approaches to obtain NPs efficient for MH. Therefore ferrite NPs with anistropic shapes and core-shell compositions have been synthesized and they have been coated with dendron molecules suitable for biomedical applications. The colloidal stabilty of theses dendronized NPs have been investigated in different physiological media and their MRI and MH properties have been assessed performing respectively relaxivity and SAR measurements. An in vitro study has determined their cytotoxity and their shape dependent cellular uptake. The cellular uptake has been followed as a function of the NPs concentration and the presence or not of a magnetic field. The effect of MH as a function of the NPs concentration and NPs design is then discussed.

R.01.5
15:05
Authors : Ali Ghafarinazari (1), Gianni Zoccatelli (2), Erica Locatelli (3), Mauro Comes Franchini (3), Marina Scarpa (4), Nicola Daldosso (1)
Affiliations : (1) Computer Science Department, University of Verona, Verona, Italy (2) Department of Biotechnology, University of Verona, Verona, Italy (3) Department of Industrial Chemistry, University of Bologna, Bologna, Italy (4) Department of Physics, University of Trento, Trento Italy

Resume : Light emission of porous silicon (pSi) particles is well-known to be sensitive to quenching due to surface oxidation. To avoid this, surface functionalization leads to stabilize the optical emission in ethanol for years [1]. However, the possible applications in Medicine are severely limited because of the incompatibility with biological solutions. Light emitting pSi particles were prepared by anodization of Si wafer. The pSi suspended in acrylic acid resulting in carboxyl groups as confirmed by FTIR. Polymeric covering carried out by covalent conjugation of PEG, and also with chitosan adsorption. For the first time, experimental results showed that pSi covered by biopolymers maintains the emission stability in in vitro conditions for more than three months without significantly affecting the optical quantum efficiency. We investigated the interaction of pSi (by different surface chemistry: native, oxidized, and functionalized by carboxyl, amine, PEG, and chitosan) with Cobinamide (Cbi) in order to test redox activity of pSi on a loaded drug. Cbi is precursor of vitamin B12 and very sensitive to decompose by redox. Up to now, proposed procedure for controlling redox of drug is pre-oxidation of pSi [2], which leads to decrease strongly light emission and porosity [3]. Our results confirmed that PEG covering leads to avoid redox of Cbi. Moreover, it leads to increase loading amount and improving release profile of the drug. Cbi improves PL stability of pSi, too. The present findings, combined to the fact that functionalized pSi particles can be up-taken by human dendritic cells without toxicity, reduction in cell viability, or immune response [1], are very promising candidates in the field of Nanotheranostics. [1] N. Daldosso, et al., J. Material Chemistry B, 2 (2014) 6345 [2] M.J. Sailor, et al., Chemical Material, 26 (2014) 2758 [3] A. Ghafarinazari, et al., Thermochimica Acta, 623 (2016) 65

R.01.6
15:20
Authors : Alexandros Lappas
Affiliations : Institute of Electronic Structure and Laser, Foundation for Research and Technology - Hellas, Vassilika Vouton, 71110 Heraklion, Greece

Resume : As the controlled synthesis of nanoscale particles advances, the need for protocols to develop complex materials with enhanced properties rises. We discuss the progress in complex colloidal systems of individual nanocrystals (NCs) arranged in tailored cluster-like structures with focus on those of iron oxide chemical origin. [1] Such size-tunable (diameter < 100 nm) nanostructures can be obtained upon careful modification of surfactant-assisted synthesis parameters, involving single-step polyol-based avenues offering a wide phase-space exploration. We show that by understanding the evolution of their properties upon the assembly of their inorganic subunits, these water-dispersible, of low-cytotoxicity colloidal nano-assemblies can address theranostic requirements. As an example, we demonstrate the effects of particle assembly as the intra-cluster degree of organization and packing density of maghemite NCs is varied, postulating to a hierarchy of length-scale dependent magnetic interactions. [2] The emergence of cooperative mechanisms (including, intra-cluster surface-spin disorder, exchange and dipole-dipole interactions) is shown to be the key in the design of biocompatible cluster-like targeted agents, with a remarkable improvement of the T2-contrast generation in MRI and increased heat dissipation capability in magnetic hyperthermia. [3] [1] A. Kostopoulou and A. Lappas, Nanotechnol. Rev. (2015); doi:10.1515/ntrev-2014-0034. [2] A. Kostopoulou et al., Nanoscale 6, 3764 (2014). [3] D. Sakellari et al., Mater. Sci. Eng. C (2015); doi:10.1016/j.msec.2015.08.023.

R.01.7
15:40 Coffee break    
 
Superparamagnetic nanoparticles as theranostic agents : Nguyen TK Thanh - M. McCommack
16:00
Authors : A. Lascialfari
Affiliations : Dipartimento di Fisica, Università degli studi di Milano, and INSTM, Milano, Italy

Resume : In the last two decades, a lot of attention was devoted to novel multifunctional nanostructures based on magnetic nanoparticles (MNP) useful as agents for Magnetic Resonance Imaging, Optical Imaging and Magnetic Fluid Hyperthermia, as carriers for drugs and molecular targeting vectors. Many systems reported by different research groups, showed high nuclear relaxivities, i.e. high efficiency in MRI contrast, and high Specific Absorption Rate (SAR). For some compounds, the possibility to collect images of the regions where the MNP are delivered through MRI and Optical Imaging, is joint to the use of radio-frequency fields that can heat locally the tumour cells, possibly inducing their apoptosis or death; a theranostic agent is thus obtained. In the field of drug delivery and molecular targeting, few examples of reproducible experiments using superparamagnetic nanoparticles are actually present in literature. All the above cases, with particular attention to the case of MRI contrast agents and the related nuclear relaxation models, will be briefly introduced and discussed.

R.02.1
16:30
Authors : Shinya Maenosono
Affiliations : Japan Advanced Institute of Science and Technology

Resume : Superparamagnetic iron oxides (SPIOs) are biocompatible and relatively easy to synthesize; these properties make them the most used magnetic nanoprobes (MNPs) in biomedicine to date. They have been studied for several decades and have contributed to both diagnostics and therapeutics. However, the relatively low saturation magnetization (MS) of SPIOs limits their potential in these applications. In addition, SPIOs are single-function MNPs, and thus the use of SPIOs in biomedicine has not been rapidly expanded. Considering the characteristic size of biological systems, MNPs with smaller dimensions than normally used SPIOs are preferred as they would increase the spatial resolution and molecular recognition property. Using MNPs, which have smaller diameter and higher MS than SPIOs, one can improve efficiency in various applications. Moreover, these magnetically superior ultrasmall MNPs could lead to revolutionary and novel clinical applications. Recently, superparamagnetic metallic MNPs have become readily available thanks to the development of a range of synthetic techniques. In general, the metallic MNPs exhibit higher magnetic properties than SPIOs, and thus those metallic MNPs increasingly attract attention in biomedicine. In addition, various heterostructured multi-functional metallic MNPs including magnetic-fluorescent and magnetic-plasmonic hybrid MNPs have been recently developed for biomedical separation/imaging. We review the progress of research on biomedical MNPs.

R.02.2
16:50
Authors : Nanasaheb D. Thorat1,3, Mohamed Radzi Noor2,3, Edel Durack2,3, Tewfik Soulimane2,3? Syed A.M. Tofail1,3
Affiliations : 1 Department of Physics & Energy, University of Limerick, Limerick, Ireland 2 Chemical & Environmental Sciences Department, University of Limerick, Limerick, Ireland 3 Materials & Surface Science Institute, University of Limerick, Limerick, Ireland

Resume : Nanoparticle-based cancer theranostics represent an emerging and novel approach to cancer treatment. The unique properties of nanoparticles, such as small size, large surface area, multifunctional groups available on surface, facilitate their applications in cancer treatment compared to classical pharmaceutics. Cancer hyperthermia based on magnetic nanoparticles is one of the great advantageous treatment and overcomes drawbacks of established cancer therapies. It deals with thermal ablation of cancer cells at temperature between 42?45 oC preferentially eradicate them through an expeditive apoptotic cell death without damaging normal tissues. Unique advantages of hyperthermia using nanomaterials include spatiotemporally controlled treatments of targeted diseases in a noninvasive manner. However, cancer hyperthermia possesses extreme challenges including the diagnostic sensitivity, treatment efficacy, and bioavailability of nanoparticles as well as the heterogeneity and drug resistance of tumors for eventual clinical implementation. In our current project, we aim to introduce novel magnetic-platinum core-shell nanosystem as a tumor pH-sensitive drug carrier for effective cancer theranostics. The developed core-shell system consists of two subunits, first is magnetic (Fe3O4) core with platinum shell (Pt), Pt shell improves hyperthermia performance of magnetic nanoparticles. The second is surface modalities of core-shell system that can allow anticancer drug and deliver it into cancer cells with temperature and pH. The developed system can deliver drugs and overcome cancer drug resistance through combined effect of magnetic hyperthermia and controlled drug release. The two functions are designed to be triggered only by the heat generated through the application of an alternating magnetic field (AMF). We have successfully visualized cancer cells by using these core-shell nanostructures before and after hyperthermia via a T2 MR imaging. Cancer cells incubated with these core-shell nanoparticles are detected in MR imaging, demonstrating early stage diagnosis of tumors without using any targeting agents. Furthermore, combined hyperthermia and pH-triggered drug release enabled efficient hyperthermia to selectively kill cancer cells. In particular, we demonstrated the superior therapeutic efficacy of core shell nanostructure in highly heterogeneous drug-resistant tumors, showing a great potential for further clinical applications.

R.02.3
17:05
Authors : G. Ori, M. Boero, C. Massobrio
Affiliations : Institut de Physique et Chimie des Matériaux de Strasbourg, Université de Strasbourg et CNRS - UMR 7504, 23 rue du Loess 67034 Strasbourg Cedex 2, France

Resume : Nanoparticles realized from molecular building blocks are a common denominator for a wide spectrum of nanotechnological and biomedical applications. The practical realization of nano-objects assembly relies on the precise understanding of the nature of the fundamental interactions occurring at the surface of a single nano-object and its surrounding microenvironment. Iron oxides, particularly magnetite (Fe3O4) and maghemite (γ-Fe2O3), have attracted interest in numerous fields including environmental remediation, biophysisics, spintronics devices and theranostic applications. However, the study of hybrid interfaces between iron oxide and organic ligands (used for their sinthesis and functionalization) remains in its infancy. The electronic structure of iron oxides varies qualitatively depending on the surface orientation and termination. Here, as a first step towards ultimately exploring organic ligand-iron oxides interfaces, we focus on the theoretical description of the electronic and magnetic properties of Fe3O4 and γ-Fe2O3. We present a comprehensive investigation, via first-principles molecular dynamics combined with density functional theory (DFT) calculations, of various iron oxides surface terminations. We compare several properties such as structural stability, electronic structure and spin moment topology among different surface terminations.

R.02.4
17:20
Authors : Mari Takahashi, Priyank Mohan, Koichi Higashimine, Akiko Nakade, Derrick Mott, Tsutomu Hamada, Kazuaki Matsumura, Tomohiko Taguchi, Shinya Maenosono
Affiliations : Japan Advanced Institute of Science and Technology; The University of Tokyo

Resume : Intracellular membrane vesicles transport proteins and lipids between subcellular organelles and are essential for a variety of cellular processes. Thus, the impaired formation in intracellular membrane vesicles often result in severe diseases. Understanding the exact composition of proteins and lipids in intracellular membrane vesicles may provide the clue to cure diseases caused by the impaired membrane transport. Magnetic separation is thought to allow the identification of proteins and lipids, however, there are several requirements for the magnetic probes. First, their size should be small enough compared to the size of the vesicle. Secondly, they should have excellent magnetic properties. Finally, they should have an imaging capability. To meet these criteria we developed magnetic-plasmonic hybrid Ag@FeCo@Ag core@shell@shell nanoparticles (NPs). The NPs enable us to do real-time plasmonic bioimaging which can tell us the timing of magnetic separation even when the intracellular vesicles are transient during the magnetic separation. The surface of the Ag@FeCo@Ag NPs were functionalized with biocompatible polymer which was made of poly-L-lysine. The magnetic separation and plasmonic imaging capabilities of the NPs were demonstrated using both liposomes and actual cells.

R.02.5
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Design of nanotherapeutics (1) : B. Kalska-Szostko - M. Farle
08:30
Authors : Teresa Pellegrino
Affiliations : Drug Discovery and Development Department, Italian Institute of Technology, via Morego 30, 16163, Genoa (Italy) e-mail: teresa.pellegrino@iit.it

Resume : The use of heat to reduce tumor mass is very ancient. Nowadays there are many techniques that allow to focalize the heat in very specific body regions resulting in treatments that are more efficient and minimize side effects. Inorganic Nanoparticlesdue to their nanoscale size,which confer unique physical-chemical features enable their use as heat hubs with external activation. At the same time, given the high surface to volume ratio, the surface of such tiny nanoparticles can be functionaled with biomolecules (i.e. proteins, vitamins, small ligands, etc.) enabling tumor targeting, or with polymer shell for carrying drug molecules and release them under controlled stimuli. Here, two examples of functionalized nanoparticles that can be activated by alternating magnetic field or by near infrared light will be reported. I will first focus on our recent progress on iron-based nanoparticles as heat mediators in magnetic hyperthermia and heat mediated drug carriers (Guardia et al, J. Mat. Chem. B, 2014, 2, 4426, Kolosnjaj-Tabi, ACS NANO, 2014, 8, 4268). Later, I will report about chalcogenide-based nanoparticles as plasmonic nanoparticles for photo-ablation and detection based on Cu64radiolabelling (A. Riedinger, JACS., 2015, 137 151454). Acknowledgements: The author acknowledges the ItalianAIRC project (Contract No. 14527), the Cariplo foundation (Contract No. 2013 0865) and the EU-ITN network Mag(net)icFun (PITN-GA-2012-290248)

R.03.1
09:00
Authors : Emanuele Papini, Fabrizio Mancin
Affiliations : Dipartimento di Scienze Biomediche, Università di Padova, via U. Bassi 58/B, Padova, 35131, Italy Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, Padova, 35131, Italy;

Resume : Over the last few years, silica nanoparticles have attracted a great deal of interest as materials for biomedical applications. At first glance, this may appear quite surprising. Unlike other nanomaterials, silica nanoparticles do not have any nanosize-related properties. Their peculiarity lies in their highly cross-linked polymeric nature. Thank to this, they are much more rigid than other polymeric nanoparticles. This makes it possible to process them into very complex structures, including mesoporous particles, nanoshells and multi-shell particles. Moreover, they can accommodate in their interior (either in the silica matrix or within pores) active molecules, such as drugs, dyes and photosensitizers. Also the surface can be functionalized with other organic molecules as polymers and targeting agents. Notably, silica does not need to be made only by silicon oxide. Using organosilane precursors in the formation of the silica network, organically modified silica (ORMOSIL) materials can be obtained. In the last years, we have focused our attention in exploiting the self-organized nature of silica and ORMOSIL nanoparticles to develop smart nanovehicles for biomedical applications. The used of appropriate precursors and synthetic protocols allowed us to produce multifunctional nanosystems where the components are specialized not only by their chemical nature but also by their topological organization. High nanosystems specialization is necessary to cope with the complexity of the biological environment where there are aimed to operate. A deed investigation of the events and interactions a silica nanoparticle undergoes when exposed to biological fluids and entities has revealed that several, sometimes neglected, actors are at play. Nanoparticles adsorb proteins, stimulate immune response, are captured by macrophages and similarly specialized cells, interact with cellular membranes and receptors, release their payload. In this lecture, we will shortly discuss the our approach on the self-organization of multifunctional silica nanoparticles and the lessons we learned on the interaction between such nanosystems and biological entities.

R.03.2
09:20
Authors : A. Loiseau1, J.Boudon1, C.Mirjolet2, G. Créhange2, B. Collin2, A. Oudot2, S. Roux3, N. Millot1
Affiliations : 1 Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303 CNRS-Université Bourgogne Franche-Comté, 21078 Dijon cedex, France; 2 Centre Georges-François Leclerc, 21079 Dijon cedex, France; 3 Institut UTINAM, UMR 6213 CNRS-Université Bourgogne Franche-Comté, 25030 Besançon cedex France

Resume : Titanate nanotubes (TiONts) are synthetized by a hydrothermal process (Papa et al., 2009). Their uncommon morphology obtained by controlled parameters allows them to be internalized more easily into cells. This permits their use as novel transfection agents (Papa et al., 2013) without inducing cytotoxicity while providing a radiosensitization effect (Mirjolet et al., 2013). These TiONts are combined to a therapeutic molecule which is docetaxel (DTX) widely used for the treatment of prostate cancer. Currently, injected drugs only reach very weakly tumor sites. Thus, high doses relative to the patient?s requirement are administered causing harmful side effects. In the last decade, the development of nanotechnologies has offered a new strategy to vectorize an active substance specifically in diseased cells. In this work, two developments of nanohybrids are presented to fight against prostate cancer cells and a particular attention was paid on the elaboration of functionalized-TiONts nanohybrids. The first approach consists in combining TiONts and DTX by an original pathway. In vitro results on human prostate cancer cell lines and results of in vivo SPECT-CT images will be presented as well as first irradiation tests. In a second one TiONts and gold nanoparticles, which confers a therapeutic effect by hyperthermia while being detectable by X-ray imaging and MRI (Alric et al., 2008), are combined together. In this context, functionalized-TiONts appear as versatile nanovectors. A.-L. Papa et al., J. Phys. Chem. C, 113 (2009) 12682?12689 A.-L. Papa et al., Nanotoxicology, 7, 6 (2013) 1131-1142 C. Mirjolet et al., Radiother. Oncol., 108, 1 (2013) 136-142 C. Alric et al., Gold Bulletin, 41, 2 (2008) 90-97

R.03.3
09:40
Authors : N. Griffete, J. Fresnais, A. Espinosa, C. Wilhelm, A. Bée, C. Ménager
Affiliations : N. Griffete, J. Fresnais, A. Bée, C. Ménager Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire PHENIX, Case 51, 4 place Jussieu, F-75005 Paris, France. A. Espinosa, C. Wilhelm MSC, UMR CNRS 7057, University Paris Diderot, 75205 Paris cedex 13, France.

Resume : Magnetic nanoparticles (MNPs) have attracted considerable attention for magnetic targeting and hyperthermia applications owing to their ability to generate heat when exposed to an alternative mag-netic field (AMF) without penetration depth limit. Novel magnetic materials for therapeutic agents re-lease based on thermosensitive polymers or vesicles have been developed. In this case, the approach was to induce an increase of permeability of the vector by heat dissipation under AMF excitation. Another way to release drug is to use hyperthermia to break bond between superparamagnetic iron oxide nanoparticles and the target in presence of oscillating magnetic fields. Recently, multifunctional ligands linked to iron oxide nanoparticles took benefits from local heating of nanoparticle’s surface to release a fluorophore on demand. Our approach is motivated by these last developments, i.e. to use local heating as the key parameter to trigger drug release. We synthesised an innovative magnetic delivery nanodevice for targeted cancer therapy showing active control over drug release by using hyperthermia effects. Our material, wich combines the drug controlled release ability of non thermosensitive Molecularly Imprinted Polymers (MIP) with magnetic properties of iron oxide nanoparticles, allows the control release of dox-orubicine. Upon AMF exposure, the bonds between the MIP and the doxorubicin are broken and the molecule is released without any significant heating of the medi-um. These materials offer great promise for the doxorubicin release under alternating magnetic field but moreover we think that this approach can be expanded to other polymers or molecules. Using Magnetic molecularly imprinted polymers for drug delivery under AMF is a major advance in the development of multifunctional targeted drug delivery technologies and may become important theranostic tools in nanomedicines for in vitro and in vivo applications.

R.03.4
09:55
Authors : Thomas Pons, Sophie Bouccara, Sophie Pezet, Nicolas Lequeux, Vincent Loriette, Alexandra Fragola
Affiliations : Laboratoire Physique et Etude des Matériaux, ESPCI/CNRS/UPMC UMR8213, 10; rue Vauquelin, 75005 Paris

Resume : The in vivo detection of rare circulating cells using non invasive fluorescence imaging would provide a key tool to study migration of eg. tumoral or immunological cells. Fluorescence detection is however currently limited by a lack of contrast between the small emission of isolated, fast circulating cells and the strong autofluorescence background of the surrounding tissues. We present the development of near infrared emitting quantum dots with long fluorescence lifetime for sensitive time-gated in vivo imaging of circulating cells. These QDs are composed of low toxicity ZnCuInSe/ZnS materials and made biocompatible using a novel multidentate imidazole zwitterionic block copolymer, ensuring their long term intracellular stability. Cells of interest can thus be labeled ex vivo with QDs, injected intravenously and imaged in the near infrared range. Excitation using a pulsed laser coupled to time-gated detection enables the efficient rejection of short lifetime (≈ ns) autofluorescence background and detection of long lifetime (≈ 150 ns) fluorescence from QD-labeled cells. We demonstrate efficient in vivo imaging of single fast-flowing cells in small animals, which opens opportunities for future biological studies.

R.03.5
10:10 Coffee break    
 
Design of nano-objects and properties : C. Sangregorio - T. Pellegrino
10:30
Authors : Michael Farle
Affiliations : Faculty of Physics, University of Duisburg-Essen, 47057 Duisburg, Germany

Resume : Magnetism in structures with dimensions on the few - nanometer scale have been the center of many investigations ranging from topics in spin-torque and spin-injection dynamics and interactions in biomedical applications to the creation of new types of hard, soft or multi-functionalized materials. Such nanostructured “building blocks” offer new exciting possibi¬li-ties to create new artificial materials.In biological and medical technologies magnetic hybrid or functionalized particles find applications in site-targeted therapy, diagnosis, cell separation and water purification. For innovations in electromobility and wind harvesting new lightweight motors and generators are needed which require the design of new types of permanent magnets – again based on magnetic nanoscale building blocks The talk will give an introduction to the state of the art and address the challenges for tailoring the properties of such building blocks. New functionalities can be obtained based on the intelligent combination of magnetic and non-magnetic materials. Work performed within EU- networks SyntOrbMag, REFreePerMag, IMAGINE and DFG,SFB 445. - H. Zabel and M. Farle (eds.) Magnetic Nanostructures, Springer Tracts in Modern Physics 246 (2013) - Muhammad Arshad Kamran et al.,Tunable emission properties by ferromagnetic coupling Mn(II) aggregates in Mn-doped CdS microbelts/nanowires, Nanotechnology 25 (2014) 385201 - Zi-An Li et al., Chemically-ordered decahedral FePt nanocrystals, Phys. Rev. B 89 (2014) 161406(R) - Zi-An Li, et al., Electrostatic doping as a source for robust ferromagnetism at the interface between antiferromagnetic cobalt oxides , Scientific Reports 5 (2015) 7997 - Chr. Kurts, et al. Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates" Scientific Reports (2015) accepted

R.04.1
11:00
Authors : Paulo C. Morais
Affiliations : University of Brasília, Institute of Physics Brasília, Brazil

Resume : The process of reconstruction of pre-fabricated thin films comprising nanosized particles deposited onto flat substrates triggered by immersion into post-treatment solutions at increasing concentration will be presented and discussed. The evolution of the reconstruction process is assessed by measuring the time (t) dependence of the width (W) of the particle analysis histogram, the W parameter being extracted from atomic force microscopy images. Additionally, a physical picture for modeling the film reconstruction, which provides reconstruction time constants associated to single particles and small agglomerates, the key units associated to the process, ranging from 1 to 10 hours is introduced. The nanoparticle-based film reconstruction triggered by an exogenous stimulus, the use of the W versus t data to describe the process and the model picture accounting for the recorded data have not been previously reported. It is envisaged the disclosed reconstruction process is quite general and may take place in thin films fabricated from nanomaterials regardless the shape, size or chemical composition as long as the solution used for post-treatment contains chemical moieties able to bind the nanomaterial’s surface in one end and bridging together the nanosized units in the other end. Emphasis will be devoted to modulation of properties of thin films engineered for applications in nanobiosensing using the surface reconstruction process.

R.04.2
11:20
Authors : JitKang Lim, SimSiong Leong, SweePin Yeap, BoonSeng Ooi, Abdul Latif Ahmad, Zainal Ahmad.
Affiliations : School of Chemical Engineering, Universiti Sains Malaysia, Nibong Tebal, Penang 14300, Malaysia

Resume : Magnetic separation is always an important feature in various biomedical application involved the utilization of magnetic nanoparticles. So far, most of the works on magnetic separation are mainly focusing on high gradient magnetic separation (HGMS). Separation of magnetic nanoparticles, especially superparamagnetic nanoparticles, at low field gradient (< 100 T/m) is extremely challenging due to the presence of thermal randomization energy and also viscous drag [1]. Here we describe our findings on the influences of colloidal forces [2] and hydrodynamic effects [3] on magnetophoresis of magnetic nanoparticles at low field gradient. The extinction profile of nanoparticles undergoing low gradient magnetic separation (LGMS) was recorded and its kinetic behaviour are interpreted based upon particle-particle and particle-fluid interaction. For particle-particle interaction, we investigate the role of colloidal forces in dictating the magnetophoretic separation kinetic of electrosterically-stabilized magnetic nanoparticles under the framework of extended-DLVO theory [2,4]. Convective current driven by momentum transfer between magnetic nanoparticles (MNPs) and their surrounding fluid during magnetophoresis process is also presented as a consequence of particle-fluid interaction [3]. We revealed two unique features of this convective flow associated to low gradient magnetophoresis, namely, (i) the continuous homogenization of the MNPs solution and (ii) accompanying sweeping flow that accelerates the collection of MNPs. According to both calculation and experimental data, the induced convection boosts the magnetophoretic capture of MNPs by approximately 30 times compared to the situation with no convection. [1] J.K. Lim, et al., ACS Nano, 2010, 5, 217 ? 226. [2] S.P. Yeap, et al., Langmuir 2012, 28, 14878 ? 14891. [3] S.S. Leong, et al., Soft Matter 2015, 11, 6968 ? 6980. [4] S.P. Yeap, et al., J. Phys. Chem. C 2012, 116, 22561 ? 22569.

R.04.3
11:40
Authors : Guorui Jin, Duo Mao, Dan Ding, Bin Liu, Kai Li
Affiliations : Institute of Materials Research & Engineering, A*STAR, 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634; Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, China 300071; Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, China 300071; Institute of Materials Research & Engineering, A*STAR, 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634; Institute of Materials Research & Engineering, A*STAR, 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634

Resume : Stem cell-based therapies hold great promise in providing desirable solutions for diseases that cannot be effectively cured by conventional therapies. To maximize the therapeutic potentials, advanced cell tracking probes are essential to understand the fate of transplanted stem cells without impairing their properties. Herein, we introduce conjugated polymer (CP) nanodots as non-invasive fluorescent trackers with high brightness and low cytotoxicity for tracking of mesenchymal stem cells (MSCs) to reveal their in vivo behaviours. As compared to the most widely used commercial quantum dot tracker, CP nanodots have shown significantly better long-term tracking ability without compromising the features of MSCs in terms of proliferation, migration, differentiation and secretome. Fluorescence imaging of tissue sections from full-thickness skin wound-bearing mice transplanted with CP nanodot-labeled MSCs suggests that paracrine signaling of the MSCs residing in the regenerated dermis is the predominant contribution to promote skin regeneration, accompanied with a small fraction of endothelial differentiation. To the best of our knowledge, this is the first time exogenous cell trackers could be used to clearly visualize the transplanted MSCs, which revealed that they did not undergo epidermal differentiation because the cells were observed to remain in the regenerated dermis without migration to the epidermis. The facile labeling approach and reliable performance using CP nanodots as long-term cell tracker is beneficial in providing valuable insights into the regenerative capacities of therapeutic stem cells, especially those cells with difficulties in transfection to express fluorescent proteins or luciferase.

R.04.4
11:55
Authors : Majid Ebrahimi1, Serge Ostrovidov1, Sahar Salehi1, Ali Khademhosseini1,2,3,4,5,6
Affiliations : 1 WPI-Advanced Institute for Materials Research, Tohoku University, Japan; 2 Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 3 Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; 4 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA; 5 Colleges of Animal Bioscience and Technology, Department of Bioindustrial Technologies, Konkuk University, Hwayang-dong, Kwangjin-gu, Seoul, Republic of Korea; 6 Departments of Physics, King Abdulaziz University, Jeddah, Saudi Arabia

Resume : Engineering functional muscle tissue is beneficial for treating various debilitating disorders including myopathy, traumatic injury and malignant tumor extraction through regenerative medicine approaches. However, bioengineered muscles are far in their function compared to those of the natural muscle tissues. Here, we utilized microfluidic spinning to fabricate photocrosslinkable gelatin methacryloyl (GelMA) hydrogel fibers for muscle reconstruction with improved functionalities. Furthermore, we investigated whether the application of topographical cues by surface micropatterning and chemical stimulation by soluble agrin, a neural acetylcholine receptor (AChR) cluster-inducing factor, would facilitate formation and maturation of bioengineered skeletal muscle tissue. Upon culturing cells on the patterned fibers, we observed that C2C12 myoblasts aligned compared to non-patterned fibers. Furthermore, myoblasts cultured on the patterned fibers showed improved differentiation and enhanced myotube formation as indicated by increased myotube length in comparison with those cultured on the non-patterned fibers. Moreover, the addition of agrin during differentiation period of C2C12 cells significantly increased the number and size (length) of AChR clusters on myotubes. Interestingly, combination of agrin treatment with micropatterning synergistically improved myotubes maturity as shown by increased length and aspect ratio of myotubes on the agrin treated patterned fibers. Taken together, the combination of topographical cues and agrin treatment showed to improve the maturation of myoblasts on GelMA fibers, which could be beneficial for bioengineering of enhanced muscle tissue for medical applications.

R.04.5
12:10 Lunch break    
 
Design of nanotherapeutics (2) : S. Begin - S. Soenen
13:30
Authors : Michael Giersig
Affiliations : Freie Universität Berlin, Institute of Experimental Physics, Berlin, Germany

Resume : In this lecture I will focus on advances in the diagnosis and therapy of cancer associated with the use of specific nanomaterials as products newly emerging nanotechnology. Nanotechnology allows as to manipulate matter at the level of individual atoms and produce materials with new properties that differ from their counterparts in the solid state. Recently, products based on nanotechnology help early diagnosis and treatment of diseases difficult to treat by conventional methods. One of the essential characteristics of nanomaterials is the ability to reach certain cancer cells. Compared with conventional medicines, nanotherapeutics are more effective, safer and allow personalization of the treatment. During the lecture we will presented recent advances in the manufacture of nanostructures and nanomaterials, their specific characteristics and their practical application with examples of pioneering research laboratories and our preliminary studyin the therapy of cancer.

R.05.1
14:00
Authors : Vincenzo Amendola
Affiliations : Department of Chemical Sciences University of Padova 1, Via Marzolo I-35131 Padova - ITALY

Resume : The integration of multiple functionalities in a single object with nanometric size is crucial for the development of efficient tools for nanomedicine applications. In particular, gold nanoparticles (Au NPs) have been intensively exploited as the starting component for the realization of sophisticated nanomedicine agents, where the desired functionalities are conferred by surface conjugation of various substances such as hydrophilic polymers, proteins for selective targeting, organic molecules with specific spectroscopic fingerprints or stimuli-responsive drugs.1 However, the space available on Au NPs surface is limited and only a finite number of the desired new functions can be hosted. We recently investigated a different approach to the design of Au NPs-based nanomedicines, in which new physical properties are added by doping the gold crystalline lattice to obtain an alloy. This approach, which is usually complicated by thermodynamic constraints and synthetic challenges, becomes accessible by laser ablation synthesis in solution (LASiS). LASiS operates out of thermodynamic equilibrium because NPs are obtained by laser ablation of a solid target immersed in a liquid solution.[1] Here we will present some examples of gold-based multifunctional structures and, in particular, we will focus on binary metal alloys in which the plasmonic properties of gold are combined with the magnetic properties of iron.[2] By acting on the composition of these nanoalloys, one can obtain several properties desirable for a nanomedicine agent, such as simultaneous contrast ability for magnetic resonance imaging, x-ray absorption computed tomography and Raman imaging, or superior plasmon absorption for photothermal applications, or even biodegradability. Besides, these alloys retain the surface chemistry of gold, which is fully exploitable for conjugation with thiolated molecules. Overall, the LASiS approach can be exploited for the realization of a library of multifunctional doped Au NPs and other nanoalloys of interest for nanomedicine applications. [1] a. Laser ablation synthesis in solution and size manipulation of noble metal nanoparticles, Phys. Chem. Chem. Phys., 2009, 11, 3805-3821. b. What controls the composition and the structure of nanomaterials generated by laser ablation in liquid solution?; Phys. Chem. Chem. Phys., 2013, 15, 3027-3046. [2] a. Coexistence of plasmonic and magnetic properties in Au89Fe11 nanoalloys, Nanoscale, 2013,5, 5611-5619. b. Strong dependence of surface plasmon resonance and surface enhanced Raman scattering on the composition of Au?Fe nanoalloys, Nanoscale, 2014,6, 1423-1433. c. Magneto-Plasmonic Au-Fe Alloy Nanoparticles Designed for Multimodal SERS-MRI-CT Imaging, Small, 2014, 10, 2476?2486. d. Superior plasmon absorption in iron-doped gold nanoparticles, Nanoscale 2015,7, 8782-8792 e. Laser generated gold nanocorals with broadband plasmon absorption for photothermal applications, Nanoscale, 2015,7, 13702-13714

R.05.2
14:20
Authors : Hossam Haick
Affiliations : The Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion ? Israel Institute of Technology, Haifa 3200003, Israel

Resume : The analysis of volatile organic compounds in exhaled breath samples represents a new frontier in medical diagnostics because it is non-invasive and potentially inexpensive. However, this approach has been impeded by the need for expensive equipment, the high levels of expertise required to operate such instruments, the speed required to conduct sampling and analysis, and the need for preconcentration techniques. Several advances in the knowledge and development of sensors must occur before breath testing can become a clinical reality. Sensing matrices based on nanomaterials are likely to become a clinical and laboratory diagnostic tool because they are significantly smaller, easier-to-use, and less expensive than spectrometry of or spectroscopy technique. An ideal nanomaterial-based sensor for analyzing volatile organic compounds should be sensitive at very low analyte concentrations in the presence of environmental or physiological confounding factors. It should also respond rapidly and differently to small changes in concentration and provide a consistent output that is specific to a given exposure. When not in contact with the analyte, the sensor should quickly return to its baseline state or be simple and inexpensive enough to manufacture large numbers of disposable units. The present tutorial lecture pays attention to the technological gaps and confounding factors related to nanomaterial sensor-based breath testing, in the hope of directing future research and development efforts towards the best possible approaches to overcoming these obstacles. The tutorial discusses breath testing as a complex process involving numerous steps, each of which has various possible technological alternatives with advantages and drawbacks that might affect the performance of the nanomaterial-based sensors that lie at the heart of the breath testing system. With this in mind, different ways to choose nanomaterial-based sensors and the related surface modifications are discussed, while considering the profile of the targeted breath markers and the possible limitations of the applied sensing approach, and going hand in hand with the choice of the surrounding breath-testing setup. The account will also discuss how the dynamic range and selectivity of the applied sensors can be tailored to detect pre-evaluated breath and disease-related volatile organic compounds. Based on these aspects, the account will describe the benefits and implications of using nanomaterial-based sensors for breath testing and suggest ways to overcome these obstacles, either through approaches concerning the improvement of the sensing elements or through supporting techniques such as preconcentration and dehumidification techniques.

R.05.3
14:35
Authors : Mathilde Ménard1,2, S. Begin-Colin, Cristina Blanco-Andujar1, Forent Meyer2, Damien Mertz1,
Affiliations : 1Institut de Physique et de Chimie des Matériaux de Strasbourg (IPCMS), UMR CNRS 7504, 23 rue du Loess, 67034 Strasbourg. *E-mail : damien.mertz@ipcms.unistra.fr 2 INSERM U1121 Biomatériaux et Bioingénierie, 11 rue Humann, 67085, Strasbourg

Resume : The blossoming growth of nanotechnologies has brought challenging innovations in the synthesis of multifunctional nanoparticles (NPs) for medicine, called ?nanotheranostics? (i.e.) combining diagnosis and therapy [1]. Among functional NPs for theranostic applications, superparamagnetic iron oxides (SPION) NPs are of particular interest because they are biodegradable, FDA-approved, and commercially used as T2-contrast agents for magnetic resonance imaging (MRI) [2]. Moreover, a new area of clinical application displaying a rapid expansion today is magnetic hyperthermia (MH) [3]. When exposed to alternating magnetic fields, magnetic NPs release heat locally, which affects the viability of cancer cells. However, the combination of MH with drug delivery in a unique nanoplatform is still an important scientific lock to leverage to envision clinical applications. Further, innovative strongly anchored and biocompatible nanocoatings of SPION NPs loading and releasing high payloads of drugs are crucially needed. In this work, we developed novel hybrid magnetic core-mesoporous silica nanoparticles loaded with antitumoral agents (doxorubicin, DOX), covered by a human serum albumin (HSA) shell which ensures biocompatibility, stealthiness and biodegradability [4]. The synthesis consists first in the formation of a mesoporous silica shell (~3 nm pore size, 20 nm thickness) around SPION NPs (10 nm diameter). DOX is loaded by impregnation into the small pores of the silica shell and the original grafting of isobutyramide (IBAM) binders [5] at the silica shell surface ensures a tight HSA coating and an efficient encapsulation of DOX. Further, incubation of the DOX-loaded hybrid HSA-coated core-shell NPs in protease media mimicking intracellular lysosomes allowed efficient HSA biodegradation and subsequent DOX release demonstrating the efficient bio-responsive property of such theranostic NPs. These new theranostic magnetic hybrid NPs are currently assessed in various biological studies (ca. cell viability/toxicity, cell uptake, intracellular behavior). References: 1. Adv. Drug Delivery Rev. 2010, 62, 1052-1063; Acc. Chem. Res. 2011, 44, 1029-1038; Chem. Soc. Rev. 2012, 41, 2656-26729. 2. Adv. Drug Delivery Rev. 60, 1252?1265, 2008; Acc. Chem. Res. 44,863?874, 2011; Adv. Drug Delivery Rev. 63, 24?46, 2011. 3. Int. J. Hyperther. 2013, 29 (8), 810-818; J. Neurooncol 2011, 103 (2), 317-324. 4. J. Controlled Release, 2008, 132, 171; J. Controlled Release, 2012, 157, 4. 5. ACS Nano 2012, 6, 7584 ; J. Mater. Chem. 2012, 22, 21434; Nanoscale, 2014, 6, 11676-11680.

R.05.4
14:50
Authors : Maxime Boksebeld, Andrii Rogov, Cedric Schmidt, Luigi Bonacina, Sergei Alekseev, Alain Geloen, Vladimir Lysenko, Yann Chevolot, Eliane Souteyrand, Virginie Monnier
Affiliations : Institut des Nanotechnologies de Lyon, Ecole Centrale de Lyon, Ecully, France;GAP Biophotonics, Université de Genève, Genève, Suisse;GAP Biophotonics, Université de Genève, Genève, Suisse;GAP Biophotonics, Université de Genève, Genève, Suisse;Kiev National Taras Schevchenko University, Kiev, Ukraine;Laboratoire de recherche en cardiovasculaire, métabolisme, diabétologie et nutrition , INSA Lyon, Villeurbanne, France;Institut des Nanotechnologies de Lyon, Ecole Centrale de Lyon, Ecully, France;Institut des Nanotechnologies de Lyon, Ecole Centrale de Lyon, Ecully, France;Institut des Nanotechnologies de Lyon, Ecole Centrale de Lyon, Ecully, France;Institut des Nanotechnologies de Lyon, Ecole Centrale de Lyon, Ecully, France

Resume : Nowadays, cell imaging is a key-technique for diagnosis, especially for cancer diagnosis. However, classical fluorescence imaging techniques are limited by labels photobleaching, cell autofluorescence or limited resolution. Non Linear optical (NLO) cell imaging provides solutions to each of these drawbacks1. However, the achievement of efficient NLO cell imaging requires the development of new optical probes exhibiting NLO properties. In addition, the coupling of NLO emitters with metal nanoparticles allow to exhibit many additional properties like plasmonic properties, Two Photon Excited Luminescence (TPEL) and therapeutic effect using photodynamic and photothermic therapy. In this work, we synthesized plasmonic NLO labels by coupling tuned gold nanoparticles with SHG emitters such as silicon carbide (SiC) or potassium niobate (KNbO3). The resulting nanohybrids exhibit dual nonlinear optical signals (SHG and TPEL), good localization on cell membranes and no toxicity for healthy cells. Thus, they represent an interesting alternative to the existing fluorescent labels. Finally, to obtain efficient targeting of cancerous cells, nanohybrids were functionalized with targeting ligands. On this contribution, we will present the synthesis of these nanohybrids, the resulting cell imaging and toxicity studies on healthy cells. Finally, cancerous cell targeting will be presented.

R.05.5
15:05
Authors : Jennifer Bain, Andrea Rawlings, Lori Somner, Zainab Taher, Sarah Staniland
Affiliations : University of Sheffield

Resume : Medical researchers are developing nano-therapies which can simultaneously diagnose and treat a wide range of diseases, termed theranostic agents. Precise, biocompatible magnetic nanoparticles (MNPs) are ideal nanomaterials for magnetic nano-theranostic materials, serving as both MRI contract agents and used for magnetic drug targeting and hyperthermia treatments. Magnetotactic bacteria take up soluble iron from the environment and synthesis MNPs of magnetite within dedicated internal organelles (known as magnetosomes). These magnetosomes are highly monodispersed, with strict morphology conservation within each strain but a variety of shapes shown across different strains, showing a high degree of biological precision and control over the process. These magnetosomes are proving to be ideal nano-theranostic materials and here we will show how we can modified the magnetosomes for enhanced properties. Proteomic and genetic studies have identified a ?magnetosome island? harbouring the genes that produce proteins specifically for the biomineralisation of these magnetosomes. Here we report how we use these protein mediated chemical precipitation of precise MNP for nanomedical applications. Furthermore we have produced a range of mimics that are easier to express and purified. Thus, we are building up a ?toolbox? of protein additives for tailored magnetite MNP synthesis. Finally, we are developing artificial magnetosomes. Taking inspiration from the magnetotactic bacteria, we are precipitating MNPs MNP into lipid and polymer vesicles to make magnetoliposomes/magnetopolymersomes. Interestingly we can form MNPs within the membrane or within the core more analogue to the natural magnetosomes. We will discuss how this can be achieved and controlled using electroporation and the incorporation of magnetotactic bacterial biomineralisation proteins and report their nanomedical capability.

R.05.6
15:25 Coffee break    
 
Nanoparticles toxicity : B. Kalska-Szostko - M. Giersig
16:00
Authors : Bella B. Manshian, Uwe Himmelreich, Stefaan J. Soenen
Affiliations : Biomedical MRI Unit/MoSAIC, Department of Imaging and pathology, KULeuven O&N1, Herestraat 49, B3000 Leuven

Resume : In our current society, nanotechnological applications in health care and industry are blooming, In health care, nanomaterials (NMs) have a lot of potential in the field of imaging contrast agents or targeted delivery of therapy. Although a few types of NMs are being explored in clinical trials[1], their translation from lab to the clinic remains very limited, in part owing to the pertaining uncertainties regarding their safety. More pre-clinical research needs to be performed to keep up with the pace with which novel NMs are being developed[2]. The field of nanotoxicology is a recent field which is rapidly developing into a more mature scientific research area. In its current state, the field suffers from several shortcomings such as the lack of standardization, and the need for more robust and rapid screening methods under physiologically relevant conditions. Here, we present some recent developments on evaluating NM toxicity screening through high-content based imaging combined with gene expression. The methods enable us to 1) link NM safety and biomedical relevance[3,4], 2) link NM safety to cellular NM concentrations up to the single cell level[5] and 3) evaluate specific parameters in detail (e.g. NM degradation). Making use of these detailed data, we are then able to design more safe NMs as well as develop manners to exploit their toxicity specifically on the level of tumor cells as a novel alternative anti-cancer therapy. References. 1. Schütz, C. A. et al. Nanomedicine 2013, 449. 2. Nel, A. et al. Acc. Chem. Res. 2013, 607. 3. Manshian, B. et al. Biomaterials 2014, 9941. 4. Manshian, B. et al. ACS Nano 2015, 10431. 5. Manshian, B. et al. Sci. Rep. 2015, 13890.

R.06.1
16:30
Authors : M. Simon,1 Q. Le Trequesser,2 M. Lavenas,2 G Devès1, Ph. Barberet1, H. Seznec,1 M-H. Delville2*
Affiliations : 1 CNRS Univ. Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France 2 CNRS, Université de Bordeaux, ICMCB, Pessac, France

Resume : Nanoparticles and their control are of great interest from both academic and industrial points of view, with numerous applications in domains such as medicine, catalysis and material sciences. This talk will stress on metal oxide nanoparticles (NPs) and two aspects: their use as multifunctional contrast agents to help in therapy but also their potential nanotoxicity. As multifunctional contrast agents, they can provide a multiple targeting and visualisation of organs or cells with both detectable changes in the MR signal intensity of the target tissue or organ by changing its MR relaxation properties and classical detectable optical signals for example.The development of biocompatible nanoparticles with an external shell of high-spin paramagnetic lanthanide contrast agents like gadolinium chelate, and europium fluorescent probes led to targeted imaging and gene therapy. A second aspect of NPs is their nanotoxicology which also attracted the attention of public & governments worldwide. Scientists are concerned by addressing the special characteristics of NPs in terms of toxicology and more especially assessing their biological effects. There is an urgent need to evaluate the risks of these particles to ensure their safe production, handling, use, and disposal. In particular, the behavior of NPs inside living cells is still an enigma, and no metabolic responses induced by these particles are understood so far. With this respect, we have examined the potential toxicity due to exposure of TiO2 NPs used in sunscreens & cosmetics. We applied an original imaging methodology (Ion Beam Analysis, TEM, & Confocal microscopy) to in vitro and in vivo studies, combining technologies for detection, tracking, and quantifying TiO2 NPs as well as the use of indicators for ion homeostasis, cell metabolism, or cell fate.

R.06.2
16:50
Authors : Jin Yu, Soo-Jin Choi
Affiliations : Department of Food Science and Technology, Seoul Women's University, Republic of Korea

Resume : ZnO nanoparticles have been applied in various areas, such as electronics, cosmetics, medicine, and foods. In particular, ZnO nanoparticles have been used as a zinc supplement and can be also utilized for food packaging as an antimicrobial agent. Although many recent studies have investigated cytotoxicity, toxicity, and biokinetics of ZnO nanoparticles, conflicting results have been reported, thus their potential toxicity after long-term exposure still remains to be elucidated. In this study, the toxicity of ZnO nanoparticles was evaluated by transcriptomic and proteomic analysis after repeated dose 14-day oral administration to rats. Furthermore, bulk sized ZnO nanoparticles and ZnCl2 were also administered in the same manner to compare size and ionized effects. Biological interaction between bulk- or nano-sized ZnO and biological matrices as well as in vivo dissolution property was also evaluated to determine biological fate of two different-sized particles. The results showed that nanocorona profiles binding to ZnO and transcriptomic response analyzed by next-generation sequencing were highly dependent on particle size or biological fate, although no significant toxic effects were found after repeated oral administration. These findings will provide critical information about the toxicity mechanism of ZnO nanoparticles and be useful to understand and predict their toxicity potential.

R.06.3
17:05
Authors : I.A. Birtoiu1, C. Rizea2, M.I. Rusu3, N. D. Becherescu-Barbu4, B. A. Vitalaru1, D. Togoe1, M. Pascal1,R. Munteanu1, M. V. Udrea3, B. Chiricuta3, A. Parau2, C.E.A. Grigorescu3
Affiliations : 1.Faculty of Veterinary Medicine-University of Agronomic Sciences and Veterinary Medicine; 2.ROXY VETERINARY S.R.L. Magurele, Romania; 3.National Institute of Research and Development for Optoelectronics INOE 2000, Magurele, Romania; 4. APEL LASER S.R.L., Bucharest, Romania;.

Resume : The occurrence of tumour diseases in both animals and humans is continuously increasing. Research in nanosciences and molecular biology has put lately an intense effort to identify the aetiology factors and seek for new ways of diagnostic and targeted therapies aimed at reducing mortality and increasing chances to healing. Extensive development of cancer tumours is frequently counteracted through surgery. Assessment of a clean surgical margin is vital and a precise and rapid diagnostic down to molecule level represents a technical challenge with important clinical implications. We present a new way of using surgery instruments and surface enhanced Raman spectroscopy for ex vivo and in vivo diagnostic of clean margins in real time. Raman spectroscopy extracts chemical information with reported 100%sensitivity, 100% specificity and overall accuracy of 93% in identifying carcinomas. Use of surface plasmon activity of silver versus gold nanostructures involved in the surgery instrumentation is investigated in terms of intensity and resolution of the Raman signal. Operation of10 patients (cats and dogs) were assisted with a visible (632nm) excitation source for the Raman effect. The margin diagnostic results were compared with histopathology and anatomic pathology analyses. Excellent resolution and no fluorescence background were remarked. Acknowledgment.This work has been supported from PCCA 2013-Contract 20/2014 and the National CORE programme of Romania.

R.06.4
17:20
Authors : Michele Zanoni (1), Dimitri Scholz (2), Eoin Casey (1)
Affiliations : 1. School of Chemical and Bioprocess Engineering, 2. Conway Institute, University College Dublin, Belfield, Dublin 4, Dublin

Resume : Enzyme-functionalized gold nanoparticles play a potentially important role in the development of functional materials. The chemical functionalization of gold nanoparticles is virtually unlimited ranging from organic units, to enzymes or proteins. Although the activity of biochemically active nanoparticles is widely known in sensors or as analytical tools, enzyme-functionalized nanoparticles have only recently been applied against biofilms. Biofilms are recognized as playing a critical role in fouling abiotic surfaces, with some serious negative impact for many healthcare and industrial applications. In this work the antibacterial activity of Proteinase K functionalized nanoparticles was studied using techniques from bacteriology, spectroscopy, confocal and transmission electron microscopy (TEM) and by flow cytometry. Antibacterial activity was assessed against biofilms generated by P. fluorescens bacteria. The objective of the present study was to clarify the activity of these biochemically-engineered systems on the widest number of substrates available including gram negative and positive bacteria. The key target and the most intriguing opportunity of these bioactive gold nanoparticles is a consistent, recoverable and environmental-friendly action against bacteria-fouled surfaces.

R.06.5
17:35
Authors : Jin Hu, Weiping Gao
Affiliations : Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China

Resume : Conjugating with poly(ethylene glycol) or human serum albumin is often used to increase the circulating half-lives of therapeutic proteins such as interferons, but these conjugation strategies usually lead to a heterogenous mixture of positional isomers or a fusion protein with unacceptably reduced bioactivity and low yield. To address these problems, we report a new and genetically encoded protein delivery platform, elastin-like polypeptide fusion (ELPfusion), to prolong the circulating half-life of a protein drug. We demonstrate proof-of-concept of ELPfusion by genetic fusion of an important therapeutic protein -interferon (IFN)- at its C-terminus to an elastin-like polypeptide (ELP) to form a well-defined IFN-ELP fusion protein with high yield and retained bioactivity. Notably, the circulating half-life of the IFN-ELP protein (8.6 h) was 28-fold longer than that of IFN (0.3 h). In a murine cancer model, the IFN-ELP protein showed a 65-fold increase in tumor accumulation as compared to IFN 6 h post administration. Furthermore, it completely inhibited tumor growth without appreciable toxic effect, while IFN was just slightly effective at the same dosing. These findings show that ELPfusion may provide a new solution to precisely design protein conjugates with high yield, well retained bioactivity and significantly improved pharmacological profiles.

R.06.6
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Design of theranostic nanoparticles (1) : S. Begin - D. Felder
08:30
Authors : Olivier Tillement and François Lux
Affiliations : ILM - University of Lyon 1, Lyon, France

Resume : This lecture will take place in the field of nanomedicine and will focus on a new class of ultrasmall nanoparticles (AGuIX) that can act as contrast agent for MRI and can help to deliver locally in tumors very high doses under irradiation. These nanoparticles made of a polysiloxane core and surrounded by gadolinium chelates are now synthesized with cGMP conditions for further clinical studies. They display high radiosensitizing efficiency in vitro and in vivo even at very small concentrations and for many different tumor models and irradiation types resulting in important increase of the lifespan for the animals irradiated in presence of nanoparticles. The nanoparticles can accumulate passively in tumors after intravenous injection due to enhanced permeability and retention effect. This accumulation can be followed by MRI and the best moment for irradiation can be monitored precisely. After intravenous injection, the nanoparticles are relatively rapidly eliminated by the renal way with no evidence of toxicity as shown by regulatory studies on rats and monkeys. Due to these encouraging results, AGuIX nanoparticles will be used for a phase I clinical assay on brain metastases.

R.07.1
09:00
Authors : Tatiana Da Ros
Affiliations : Department of Chemical and Pharmaceutical Sciences University of Trieste Trieste, Italy

Resume : Carbon nanostructures (CNSs), among which carbon nanotubes, graphene quantum dots, carbon nanodiamonds, play a major role in nanotechnology. Thanks to their electronic and mechanical properties, can be counted among the most promising nanomaterials in the field of molecular electronics, but they are also proving to be systems of interest in biomedicine, such as innovative materials for neuroscience and drug delivery. They can be used as building block for the preparation of new theranostic platforms. In particular the use of these structures is interesting for the possibility of multifunctionalization, both from the qualitative and the quantitative point of view. Many systems of release of anticancer drugs based on this type of nanostructures are studied in an attempt to take advantage of the ability to preferentially accumulate in tumor tissues due to the so-called EPR effect (Enhanced Permeability and Retention). In this presentation, the most significant results in this field will be presented.

R.07.2
09:20
Authors : Jianping Xie
Affiliations : Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585

Resume : In very recent years, ultrasmall metal nanoclusters with core sizes below 2 nm have emerged as a new class of functional nanoparticles due to their discrete and size dependent electronic structures and molecular-like properties, such as HOMO-LUMO transitions in optical absorption, quantized charging, and strong luminescence. Synthesis of high quality metal nanoclusters in sufficiently large quantities is necessary for establishing reliable size-property relationships and exploring their potential applications. This presentation will summarize our recent progress in the development of novel synthetic strategies for the production of atomically precise metal nanoclusters. The preparation of atomically precise metal nanoclusters is viewed as engineerable process where both the precursors (input) and their conversion chemistry (processing) may be rationally designed to achieve the desired outcome ? atomically precise metal nanoclusters (output). We will demonstrate several efficient strategies for tailoring the precursor and the conversion process, and present our understanding of the processes involved. We will also highlight some application developments of metal nanoclusters in important sustainability topics including sensors for the environment and human health, and other biomedical applications.

R.07.3
09:40
Authors : N. Francolon 1, D. Boyer 1, F. Leccia 2, E. Jouberton 3,4 , A. Walter 5, C. Bordeianu 5, A. Parat 5, D. Felder-Flesch 5, E. Miot-Noirault 3, J.M. Chezal 3 and R. Mahiou 1
Affiliations : 1 Université Clermont Auvergne, Institut de Chimie de Clermont-Ferrand, UMR 6296 CNRS / UBP / Sigma Clermont - 63171 AUBIERE 2 Université Clermont Auvergne, Génétique Reproduction et Développement, CNRS, UMR 6247, INSERM, U931 - 63000 CLERMONT-FD 3 Université Clermont Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, UMR 990, INSERM, UdA - 63000 CLERMONT-FD 4 Centre de Lutte Contre le Cancer Jean Perrin, F-63005 CLERMONT-FD 5 Université de Strasbourg, Institut de Physique et Chimie des Matériaux de Strasbourg,CNRS, UMR 7504, 67034 STRASBOURG

Resume : Currently, multifunctional nanoparticles (NPs) have become a major interest in the field of nanomedecine. These NPs may be designed for reducing the diagnosis times of some tumors and thus improving the survival rate of patients by early treatments. In this work, upconverting nanoparticles (UCNPs) based on NaYF4:Yb,Tm system were successfully dendronized for fluorescence medical imaging applications. UCNPs have attracted much attention due to their peculiar properties, relevant for bioimaging applications in the infrared range. These materials permit the conversion of near infrared (NIR) radiations into photons of higher energy (NIR or visible) via a multiphoton mechanism. In comparison with UV excitation, fluorescence imaging based on NIR light, which is only weakly absorbed by biological tissue, leads to deeper and non-invasive diagnosis.The structural, morphological and optical characterizations of resulting core/shell NaYF4:Yb,Tm@dendrons nanoparticles were performed. In vitro cytotoxicity assays have evidenced their low toxicity. In vivo fluorescence imaging study was performed in mice upon IR excitation, showing promising imaging capacities at low concentrations (0.5 mg/mL) and low power (50 mW/cm²).

R.07.4
09:55
Authors : R. Pruna, F. Palacio, M. López, A. Diéguez, M. Mir, J. Pérez, O. Blázquez, S. Hernández, B. Garrido
Affiliations : SIC, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain; SIC, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain; SIC, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain; SIC, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain; IBEC – Institut de Bioenginyeria de Catalunya, Parc Científic de Barcelona, E-08028 Barcelona, Spain; IBEC – Institut de Bioenginyeria de Catalunya, Parc Científic de Barcelona, E-08028 Barcelona, Spain; MIND-IN2UB, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain; MIND-IN2UB, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain; MIND-IN2UB, Departament d’Electrònica, Universitat de Barcelona, Martí i Franquès 1, E-08028 Barcelona, Spain

Resume : The increasing need for sensitive, low-cost and miniaturized DNA detection methods is one of the causes for the convergence of such apparently different disciplines as biochemistry and nanoscience. Traditionally, nanomaterials such as carbon nanotubes have been of primary interest for developing DNA sensors. On the other side, indium tin oxide (ITO) is a very popular material in the field of optoelectronics for its extraordinary electrical and optical properties. The present work is an investigation on the viability of developing DNA sensors based on ITO nanostructured electrodes. For this purpose, ITO was evaporated by electron beam machine onto silicon electrodes as nanostructured films. Then, a chemistry protocol was used to attach single stranded (ss-) DNA probe chains on the electrodes surface. Then, ferrocene-labeled complementary ss-DNA chains were presented to the biosensor, and the hybridization onto the sensor surface permitted their detection by cyclic voltammetry (CV), basing on reduction/oxidation (redox) properties of ferrocene molecules. Besides, the biosensor selectivity was tested by presenting ferrocene-labeled non-complementary ss-DNA chains to the DNA-functionalized surface. In this case, no hybridization was produced and hence no redox peak was detected by CV, which proved the biosensor’s selective affinity for complementary ss-DNA oligocodes.

R.07.5
10:10 Coffee break    
 
Design of theranostic nanoparticles (2) : C. Sangregorio - O. Tillement
10:30
Authors : Delphine FELDER-FLESCH (1, 2)
Affiliations : (1) Institut de Physique et de Chimie des Matériaux de Strasbourg IPCMS UMR CNRS UDS 7504 23 rue du loess BP 43, 67034 Strasbourg cedex 2 (2) Fondations FRC/Université de Strasbourg 8 allée Gaspard Monge BP 70028, 67083 STRASBOURG Cedex

Resume : Nanomedicine can take advantage of the recent developments in Nanobiotechnology research areas for the creation of platforms with superior drug carrier capabilities, selective responsiveness to the environment, unique contrast enhancement profiles and improved accumulation at the disease site. Colloidal inorganic nanoparticles (NPs) have been attracting considerable interest in biomedicine, from drug and gene delivery to imaging, sensing and diagnostics. It is essential to modify the NPs surface to have enhanced biocompatibility and reach multifunctional systems for the in vitro and in vivo applications, especially in delivering drugs locally and recognizing overexpressed biomolecules. This presentation will describe the rational design for dendrimer-nanoparticle conjugates elaboration and review their state of the art uses as efficient nanomedicine tools. REFERENCES Felder-Flesch D, Billotey C, Begin-Colin S, et al. Biomaterials, 2011, 32, 8562-8573; New J. Chem., invited Review on Dendrimers in Nuclear Medicine, 2012, 36 (2), 310-323; Eur. J. Inorg. Chem., invited Microreview on Contrast Agents, 2012, 1987-2005; Chem. Commun. 2013, 49, 9158-9160; Nanoscale 2013, 5, 4412-4421; J. Mater. Chem. B. 2014, 2, 1779-1790; New J. Chem. invited paper in SUPRABIO Issue, 2014, 38, 5226-5241; Chem. Mater. 2014, DOI: 10.1021/cm5019025; Nanomedicine Future Medicine Invited review on Dendritic tools on Nanomedicine, 2014, will be published in the April 2015 issue.

R.08.1
11:00
Authors : Jean-Olivier Durand,
Affiliations : UMR 5253, ICGM, Case 1701, Université Montpellier, Place Eugène Bataillon, 34095 Montpellier cedex 05

Resume : Mesoporous silica nanoparticles (MSN) have attracted much attention the last decade for nanomedicine applications due to their biocompatibility, flexible functionalisation, tunable pore size and diameter. We describe here MSN engineered for two-photon triggered drug delivery or photodynamic therapy, in MCF-7 breast cancer cells. The two-photon triggered drug delivery system was based on a FRET mechanism from a two-photon dye in the walls of the MSN to an azobenzene moiety in the pores of the MSN (nanoimpellers). Concerning photodynamic therapy, a two-photon photosensitizer was encapsulated in the walls of the MSN. Two-photon photodynamic therapy was performed in vitro and in vivo on mice bearing colon xenografted tumors. We also studied the use of porous silicon nanoparticles (pSiNP) functionalized with both a photosensitizer and a targeting agent. pSiNP had been shown to be degraded into non-toxic silicic acid byproducts in vivo. The multi-functionalized pSiNP studied here were able to target, image and kill cancer cells in vitro by photodynamic therapy mechanisms both with 1-photon and 2-photon excitation. Alternatively, the synthesis of disulfide-based biodegradable Periodic Mesoporous Organosilica Nanoparticles (nanoPMOs) was realized and the nanoparticles were efficient in delivering doxorubicin in cancer cells.

R.08.2
11:20
Authors : Laurent Adumeau (1), Ji Liu(1,2), Christophe Detrembleur(2), Christine Jérôme(2), Etienne Duguet(1), Gisèle Clofent-Sanchez(3), Franck Couillaud(4), Stéphane Mornet(1)
Affiliations : (1) ICMCB-CNRS, UPR 9048, University of Bordeaux, F-33600, Pessac, France (2) CERM, University of Liege, B-4000 Liège, Belgium (3) CRMSB, UMR 5536, CNRS, University of Bordeaux, F-30000, Bordeaux, France (4) EA « Molecular Imaging and Innovative Ttherapies in Oncology » (IMOTION) University of Bordeaux, F-30000, Bordeaux, France

Resume : Recent progresses in nanotechnology offer exciting opportunities in the development of promising nanomaterials for medicine and bioimaging. Among them, multifunctional nanoparticles offer plenty of applications because of their physical properties (optic, magnetic?) which allow their use as well as contrast agents, as cell labelling tools, as hyperthermia mediators and smart drug delivery systems (DDS). The common point between these nano-objects lies in their surface chemistry which has to be mastered in the aim to control their physico-chemical features in terms of non-specific binding, targeting efficiency, or drug release. This talk will stress on current surface modification strategies of multifunctional nanoparticles developed for biological applications through two topics: - The nano-bio interface engineering using nanoparticles for in vivo imaging. Their small size, similar to that of biological entities, enables the labelling of biomolecules of interest. For instance, these nanomaterials can be used for in vivo active targeting labelling and cell tracking in the frame of diagnostic or therapeutic applications. All synthesis stages have to be controlled from the inorganic cores surface modification to the conjugaison of functional ligands such as antibodies. We experienced different application fields in biology as various as tumour labelling [1], monocyte and stem cells tracking [2,3], diagnosis of the instability of atherosclerotic plaques [4], etc. - Drug Delivery Systems (DDSs) remotely triggered by magnetic induction. In this field, functionalized magnetic nanoparticles used as heat mediators for self-regulated heat release were designed [5]. Another example of DDS based on multifunctional nanoparticles made of a mesoporous matrix allowing the transport of bioactive molecules containing superparamagnetic nanoparticles will be presented [6]. This type of system provides an interesting tool for increasing the efficacy of pharmaceuticals through improved pharmacokinetics and biodistribution. References 1. F. Sonvico, Bioconjugate Chem., 16, 1181 (2005) 2. A.-K. Bouzier-Sore, NMR Biomed. 23, 88 (2010) 3. C. Lalande, Eur. Cells Mater., 21, 341 (2011) 4. M.-J. Jacobin-Vallat, NMR in Biomed., 24, 413 (2011) 5. R. Epherre, J. Mater. Chem. 21, 4393 (2011). 6. J. Liu, J. Mater. Chem B DOI: 10.1039/c3tb21229g.

R.08.3
11:40
Authors : Leigh J. Mack, MD, PhD
Affiliations : Lead Research Physician for American Biotech Labs, LLC

Resume : This study was conducted to prove the modality of action, along with efficacy and safety of Ag4O4 particles in the application of hindering the targeting and acquisition of viruses on host cells. This study also illustrates how molecular frequency can change the dynamics of viral load and illustrate through both bench and clinical trials an empirical log reduction of the virus in the patient.

R.08.4
11:55
Authors : Emilie Molina; Patrick Lacroix-Desmazes; Nathalie Marcotte; Corine Gérardin
Affiliations : Institut Charles Gerhardt UMR 5253 CNRS-ENSCM-UM, ENSCM, Montpellier, France

Resume : Silica based drug delivery systems have emerged as an important field in biomedicine. However, their development is constrained by the tricky and numerous steps for their preparation. Within that context, we aimed at developing simpler methods for preparing biofunctional mesostructured silica nanoparticles. Our strategy relies on the use of PolyIon electrostatic Complex (PIC) micelles, obtained by complexation between a neutral ionisable double-hydrophilic block copolymer (DHBC) and an oppositely charged micellization agent, as structure-directing agents of silica. Once the mesostructured silica nanoparticles are obtained, it is possible to take advantage of the pH sensitivity of the PIC assembly to release the micellization agent. Two different synthetic routes of bio-functional hybrid silica nanomaterials were developed. The first one involves the formation of a hybrid material using oligochitosan (OC) as micellization agent. It is followed by OC extraction in water by pH control, leading to a mesoporous material functionalized with complexing units of the DHBC able to further encapsulate drugs (neomycin, porphyrin derivatives). In the second approach, the micellization agent used is a therapeutic agent (antibiotics), which allows obtaining directly a hybrid mesostructure loaded with the drug, whose amount can be controlled by varying the DHBC block lengths[1]. Subsequently, release of the drugs can be achieved by controlling the pH of the extracting medium. [1] E. Molina et al. Langmuir 2015, 31, 12839

R.08.5
12:10
Authors : Emille M. Rodrigues, Diogo A. Gálico, Italo O. Mazali, Fernando A. Sigoli
Affiliations : Instituto de Química, Caixa Postal 6154, Campinas, SP, CEP 13083-970, Brazil

Resume : In cancer research, the number of scientific works searching alternative therapies for chemotherapy and radiotherapy is continuously increasing, due to the severe side effects that are associated to them. In this context photothermal (PTT) and photodynamic therapies (PDT) are interesting for cancer treatment. Upconversion nanoparticles (UCNP) are being extensively studied for this purpose. We present the synthesis and characterization of two systems of core@shell UCNP with interesting spectroscopic properties for use in PDT. UCNP were synthesized by the thermal decomposition method in the pure hexagonal phase. For the NaYbF4@NaYF4 system, the core@shell structure was characterized by TEM as a core composed mainly for the Yb(III) and a shell composed by a mixing between Y(III) and Yb(III). This sample presented the possibility of anchoring with any PS with absorption around 650 nm for PDT and simultaneous imaging in the Visible or NIR region, besides the resulting white emission under 980 nm excitation. The NaGdF4:Pr:Er:Yb@NaYF4 NP were anchored with Rose Bengal molecule that produces 1O2. The emission properties of the NP were adequated for absorption of the RB molecule and the first results of 1O2 production were made using DPBF as singlet oxygen probe. The results show that the association of the two kinds of NP here presented could be a proposal of a system for theranostic applications using only NIR (980 nm) incident radiation.

R.08.6
12:25
Authors : [1] P. Vilela, [1] A. Heuer-Jungemann, [2] A. El-Sagheer, [2] T. Brown, [3] N. Smyth, [1] A. Kanaras
Affiliations : [1] Physics and Astronomy, Institute For Life Sciences, Faculty of Physical and Applied Sciences, University of Southampton, SO17 1 BJ, UK [2] Department of Chemistry, University of Oxford, OX1 3TA, UK [3] Centre for Biological Sciences, Faculty of Medicine, Uiversity of Southampton, SO17 1 BJ, UK

Resume : mRNA is an important biomolecule due to its involvement in various diseases (e.g. cancer). Thus, lately the detection of messenger RNA (mRNA) using fluorescently labelled gold nanoparticle-oligonucleotides has been under an intense research interest as potential diagnostic tool.1 At the same time, silencing RNAs (siRNAs) have been introduced as an effective biomolecule for early treatment of diseases playing an essential role in reducing the overexpression of key proteins.2 In recent years, the use of gold nanoparticles as carrier vesicles for RNA has been shown to be a promising system for RNA delivery directly related to applications in imaging and multiplex theranostic treatments.3 In this work, we present the application of fluorescently labelled oligonucleotide coated gold nanoparticles in a complex tissue model (ex vivo skin) for the imaging and manipulation of scar tissue, which demonstrates their potential as multiplex theranostic tools. On the one hand, the oligonucleotide–gold nanoparticles sense mRNAs related to the wound healing process and on the other hand, they downregulate genes related to the expression of proteins involved in tissue scarring.

R.08.7
12:40 Lunch Break    
 
Poster session : Beata Kalska-Szostko
13:30
Authors : Anusuya Banerjee, Chloé Grazon, Yamuna Krishnan and Benoit Dubertret
Affiliations : Anusuya Banerjee; Benoit Dubertret- Laboratoire de Physique et d?Etude des Mate?riaux, ESPCI ParisTech, CNRS UMR 8213, Universite? Pierre et Marie Curie, 10 rue Vauquelin, 75005 Paris, France Chloé Grazon- Nexdot, 10 rue Vauquelin, 75005 Paris, France; Yamuna Krishnan- 929E, 57th St, E305, GCIS, Dept of Chemistry, University of Chicago, Chicago 60637, IL, USA

Resume : Quantum Dots (QDs) have emerged as novel fluorescent probes for biomedical applications.1 The photophysical properties of QDs such as broad absorption, narrow emission spectrum, reduced blinking, and enhanced photostability make them advantageous over organic fluorophores. However, for many biological applications, QDs need to be first functionalized with biomolecules such as proteins, peptides or DNA. Recently we have shown a novel method for bioconjugation of DNA and proteins to colloidal QDs coated with a zwitterionic amphiphilic polymer.2,3 Biomolecules are functionalized directly to thiols of the polymer by using bifunctional linkers. Orthogonal nature of this coupling leaves no undesirable side products. The functional properties of QDs (like high quantum yield, small size and colloidal stability) and of the biomolecules (DNA remains hybridizable and antibodies retain their recognition properties in vivo) are retained. The strategy is generalizable to large variety of biomolecules and nanoparticles. This is a robust method to generate variety of fluorescent probes for bioimaging and therapeutic applications. We are now investigating receptor mediated endocytosis of these conjugates for better evaluation as fluorescent probes. Of specific interest is the endocytosis of transferrin, for its multifaceted applications in theranostics.4 Conjugation of transferrin to QDs is carried out via (i) direct conjugation (as above) (ii) or mediated by a DNA linker. We have systematically evaluated the kinetics of endocytosis and exocytosis of these conjugates and find some striking differences in their intracellular retention and fate based on the conjugation chemistry. Some of these fascinating results will be presented herein. References: 1 I. L. Medintz, H. T. Uyeda, E. R. Goldman and H. Mattoussi, Nat. Mater., 2005, 4, 435?46. 2 A. Banerjee, C. Grazon, B. Nadal, T. Pons, Y. Krishnan and B. Dubertret, Bioconjug. Chem., 2015, 26, 1582?1589. *This work has been featured as the ACS Editors Choice Manuscript. 3 M. Tasso, M. K. Singh, E. Giovanelli, A. Fragola, V. Loriette, M. Regairaz, Z. Lenkei, N. Lequeux and T. Pons, ACS Appl. Mater. Interfaces, 2015, 26904?26913. 4 P. T. Gomme and K. B. Mccann, Drug Discov. Today, 2005, 10, 267?273.

R.9.1
13:30
Authors : Baojin Ma, Shan Zhang, Jichuan Qiu, Hong Liu
Affiliations : Shandong university

Resume : Recent years, nanomaterials have attracted more and more attention, and are widely applied in bio-field, such as bio-imaging, drug delivery and tissue engineering. In general, there are two kinds of nanoparticles: fluorescence nanoparticle and non-fluorescence nanoparticle. For most fluorescence nanoparticle, they are cytotoxicity, such as CdS, InP and so on. How to prepare biocompatible fluorescence nanoparticles for bioimaging still is a great challenge. (Fluoridated) Hydroxyapatite (FAp/HAp) is a kind of autologous material with high biocompatibility and well biodegradability. By doped with rare earth elements or combined with other inorganic fluorescence materials, FAp/HAp will possess fluorescence with relatively long life compared with common organic fluorescence materials. What?s more, fluorescence FAp/HAp also can be used as drug delivery for cancer treatment, which can be tracked in vivo. The synthetic method of FAp/HAp nanoparticles is mainly based on hydrothermal/solvothermal method, which has been developed for years. However, precisely control of nanoparticles? morphology and size is still a great problem for their practical applications. In addition, in most cases, the excited wavelength of the fluorescent FAP/HAp nanoparticles could not match the light source attached on commercial laser confocal microscopes or other equipment, which restricts their applications in bioimaging. Recently, our group have focused on synthesis and property investigation on codoped FAp nanoparticles with emitted double color at single excited wavelength, and carbon quantum dots assembled-HAp composite nanorods. We applied the nanoparticles into cell imaging and drug delivery. Further, we used these nanoparticles to modulate stem cells fate and promote cells directional differentiation. Through our work, we have gotten some important results, and believe that these multifunctional fluorescent (fluoridated) hydroxyapatite nanoparticles will have very important application in bio-field. In this talk, we will present the progress on multifunctional fluorescent (fluoridated) hydroxyapatite nanoparticles and their applications in bioimaging, drug delivery and effect on differentiation of stem cells.

R.9.2
13:30
Authors : Shan Zhang, Baojin Ma, Jichuan Qiu, Hong Liu
Affiliations : Shandong University

Resume : Inorganic nanoparticles have been applied in many fields such as drug release, cell and tissue imaging, and photo-thermal therapy. The most common used nanoparticles include silica-based nanoparticles, quantum dots nanoparticles, up-conversion fluorescent nanoparticles, nonlinear optical oxide nanoparticles, and the recently reported carbon quantum dots, graphene quantum dots and g-C3N4 quantum dots, etc. These nanoparticles complete the intracellular targeting and drug release mostly depending on the strong endocytosis of cancer cells. In general, inorganic nanoparticles cannot be degraded and will remain in the body after performing the therapy or biological functions. There is no doubt that the nanoparticles can be discharged through metabolism of circulating system, but part of them will enter the region of stem cells carried by blood. Because of the better endocytosis ability, stem cells can endocytose the nanoparticles, and these nanoparticles will in turn influence the behavior of stem cells. Therefore, the studies of the influence of inorganic nanoparticles on the fate, especially on differentiation of stem cells are of great importance for the safety evaluation of nanoparticles and most importantly for the research of reliability of the nanoparticles therapy. In addition, the regulation of stem cells fate by nanoparticle itself will also become a hot research area. In this talk, we will give a review of our recent work related to the regulation effect of nanoparticles to the fate of stem cells, and introduce several kinds of nanoparticles that have been proved to have the effect of enhancing differentiation ability of stem cells.

R.9.3
13:30
Authors : Tiberto Paola, Barrera Gabriele, Celegato Federica; Coisson Marco, Conta Gianluca, Martina Katia, Caporaso Marina, Serpe Loredana, Canaparo Roberto, Vinai Franco
Affiliations : Tiberto Paola, Barrera Gabriela, Federica Celegato, Coisson Marco, Conta Gianluca, Franco Vinai InRim, Nanosciences and Materials Dept., Torino, Italy Martina Katia, Caporaso Marina, Serpe Loredana, Canaparo Roberto Università di Torino, Neuroscienze Dept., Torino, Italy

Resume : Magnetic nanoparticles raised interest for applications in data storage, contrast agents in magnetic resonance imaging, drug delivery systems and hyperthermia [1]. The magnetic moment is exploited for target-directed delivery, detection, separation, and manipulation. The intrinsic difficulty of controlling nanoparticle dimension leads to not easily tunable magnetic properties. Bottom-down nanolithography process allows the production of nanodisks having different diameter and ferromagnetic properties. Here, the fabrication process together with magnetic behavior of Ni80Fe20 nanodisk suspended in liquid solution are presented. Fabrication is based on the self-assembling of nanospheres on Ni80Fe20 film sputtered on a resist layer [2]. The patterning process lead to a hysteresis loop having the shape typical of magnetisation vortex nucleation. Free-standing nanodisks maintain the same magnetisation behavior. To assess, in biomedical application, the suitability of the nanodisks in targeted drug delivery, chemical bioderivativation has been taken into account. Bioderivatization was aimed to the production of a nanoscaled functional material that combine multiple functionalities for enhanced therapeutic efficacy [3]. The in vitro toxicity assessment of the nanodisks will be discussed. References: [1] E. A. Rozhkova et al Adv. Mater. 2011, 23, H136?H150, [2] P. Tiberto et al., J. Appl. Phys. 113 , 17B516 (2013) [3] K.Martina et al., ACS Sust. Chem. Eng 2014, 2(11), 2595-2603

R.9.4
13:30
Authors : BEY Houda*, GTARI Wala, ASCHI Adel and OTHMAN Tahar
Affiliations : Laboratoire de Physique de la matière Molle et de la Modélisation Electromagnétique, Faculté des Sciences de Tunis, Université El Manar, 2092 Campus Universitaire, Tunis, Tunisia

Resume : Small angle light scattering (SALS) is a new technique for structural measures in a large size range, which is suitable for the study of soft matter [1]. It is a method of light scattering that bridges the gap between the broadcasting techniques standard light as dynamic or static Light Scattering (DLS and SLS) and microscopy. The sample is illuminated with an expanded beam of coherent light and a camera (CCD) monitors the intensity of the light transmitted. The image shows speckle fluctuations, which are captured by the speckle[2]. In this work, we will study the influence of physicochemical parameters (temperature, pH, pressure ...).We developed complex coacervation (protein and polyelectrolyte) that leads to the formation of microcapsules[3]. The understanding the mechanisms of formation of coacervates in different environmental conditions is essential if we are to predict and improve techno-functional properties of coacervates. Indeed, it has been shown that the functional properties of the complexed biopolymer were higher than those of the biopolymers alone and that the areas of use of these complex macromolecular assemblies were multiple. This work is widely used in many industrial applications as the development of new multifunctional food ingredients include the purification of biological molecules by precipitation, micro- or nano-encapsulation of active substances in pharmacy, medicine or cosmetology, synthesis of therapeutic vectors synthesis biomaterials biocompatible or development of biosensor. Keywords: Small Angle Light Scattering, Complex, Coacervats, Microencapsulation Référence: [1]Cipelletti L., Carpineti M.,Giglio M, Two-color cross-correlation in small-angle static light scatterin,Physical Review,53,1997. [2]Bhatia S.R, Ultra-small-angle scattering studies of complex fluids.Current Opinion in Colloid & Interface Science: 9, 404 – 411,2005. [3] Jain A.,Thakur D.,Ghoshal G. ,Katare O. P. , Shivhare U. S.,Microencapsulation by Complex Coacervation Using Whey Protein Isolates and Gum Acacia: An Approach to Preserve the Functionality and Controlled Release of β-Carotene,Food Bioprocess Technol ,8:1635–1644,2015.

R.9.5
13:30
Authors : Chun-Sing Lee
Affiliations : Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Sciences, City University of Hong Kong

Resume : Many molecular drugs, fluorescent emitters and photosensitizing agents have poor water solubility and this hinders their biomedical applications. In the past couple of decades, this problem has been successfully addressed by embedding these functional molecules into various nanometer-sized carriers including carbon nanotube, nanoparticles of polymers, mesoporous silica etc. However, the use of inert carriers can also lead to other concerns including their biodegradation and long-term side effects, in particular as the carriers often have high weight fractions (over 90%) with respect to the active organic molecules. In recent years, these functional molecules have been self-assembled into nanoparticles without using any additional inert carrier. These ?self-carried? nanoparticles intrinsically have up to 100% of the functional molecules and have good water dispersibility due to their high surface area to volume ratios. In this talk, I will summarize our recent works on preparation and biomedical applications of these ?self-carried? nanoparticles. References 1. ?Preparation and size control of sub-100 nm pure nanodrugs?, J. Zhang, Y. Li, F. F. An, X. Zhang, X. Chen, C. S. Lee, Nano Lett., 15, 313 (2015). 2. ?Self-monitoring and self-delivery of photosensitizer-doped nanoparticles for highly effective combination cancer therapy in vitro and in vivo?, J. Zhang, Y.C. Liang, X. Lin, X. Zhu, L. Yan, S. Li, X. Yang, G. Zhu, A.L. Rogach, P.K.N. Yu, P. Shi, L.C. Tu, C.C. Chang, X. Zhang, X. Chen, W.J. Zhang and C.S. Lee, ACS Nano, 9, 9741 (2015). 3. ?Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release?, J. Zhang, S. Li, F.F. An, J. Liu, S. Jin, J.C. Zhang, P.C. Wang, X. Zhang, C.S. Lee and X.J. Liang, Nanoscale, 7, 13503 (2015). 4. ?Highly stable near-infrared fluorescent organic nanoparticles with a large Stokes shift for noninvasive long-term cellular imaging?, J. Zhang, R. Chen, Z. Zhu, C. Adachi, X. Zhang and C.S. Lee, ACS App. Mater. & Inter., 7, 26266 (2015).

R.9.6
13:30
Authors : Jinfeng Zhang, Chun-Sing Lee
Affiliations : Center of Super-Diamond and Advanced Films (COSDAF) & Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR, PR China

Resume : Theranostic nanomedicine is capable of diagnosis, therapy and monitoring the delivery and distribution of drug molecules and has received growing interest. Herein, a self-monitored and self-delivered photosensitizer-doped FRET nanoparticle (NP) drug delivery system (DDS) is designed for this purpose. During preparation, a donor/acceptor pair of perylene and 5,10,15,20-tetro (4-pyridyl) porphyrin (H2TPyP) is co-doped into a chemotherapeutic anticancer drug curcumin (Cur) matrix. In the system, Cur works as a chemotherapeutic agent. In the meantime, the green fluorescence of Cur molecules is quenched (OFF) in the form of NPs and can be subsequently recovered (ON) upon release in tumor cells, which enables additional imaging and real-time self-monitoring capabilities. H2TPyP is employed as a photodynamic therapeutic drug, but it also emits efficient NIR fluorescence for diagnosis via FRET from perylene. By exploiting the emission characteristics of these two emitters, the combinatorial drugs provide a real-time dual-fluorescent imaging/tracking system in vitro and in vivo, and this has not been reported before in self-delivered DDS which simultaneously show a high drug loading capacity (77.6%Cur). Overall, our carrier-free DDS is able to achieve chemotherapy (Cur), photodynamic therapy (H2TPyP), real-time self-monitoring of the release and distribution of the nanomedicine (Cur and H2TPyP). More importantly, the as-prepared NPs show high cancer therapeutic efficiency both in vitro and in vivo. We expect that the present real-time self-monitored and self-delivered DDS with multiple-therapeutic and multiple-fluorescent ability will have board applications in future cancer therapy.

R.9.7
13:30
Authors : Rui Chen, Jinfeng Zhang, Chun-Sing Lee
Affiliations : Center of Super-Diamond and Advanced Films (COSDAF) & Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR, P. R. China.

Resume : In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive degradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy and multifunctional theranostics. Reference 1. Graphitic Carbon Nitride Nanosheet @ Metal-Organic Framework Core-shell Nanoparticles for Photo-chemo Combination Therapy , R. Chen, J. Zhang, Y. Wang, X. Chen, J. A. Zapien, C. S. Lee, Nanoscale 2015,7, 17299. 2. Optimized Metal–Organic-Framework Nanospheres for Drug Delivery: Evaluation of Small-Molecule Encapsulation, J. Zhuang, C. Kuo, L. Chou, D. Liu, E. Weerapana, C. Tsung, ACS Nano 2014, 8, 2812. 3. Enhanced Photoresponsive Ultrathin Graphitic-Phase C3N4 Nanosheets for Bioimaging, X. Zhang, X. Xie, H. Wang, J. Zhang, B. Pan, Y. Xie, J. Am. Chem. Soc. 2013, 135, 18.

R.9.8
13:30
Authors : Mi-Ran Go, Hyeon-Jin Kim, Song-Hwa Bae, Da-Eun Lee, Jin Yu and Soo-Jin Choi
Affiliations : Department of Food Science and Technology, Seoul Women's University, Republic of Korea

Resume : Inorganic nanoparticles have been widely applied to various industrial fields and biological applications. Especially, zinc oxide (ZnO) and silicon dioxide (SiO2) nanoparticles are used in various food products to improve functionality and stability as a nutritional supplement and an anti-caking agent, respectively. However, there is little information about the physicochemical properties of nanoparticles in foods and their interaction with food components or biological matrices, which can eventually affect their biokinetics and in vivo toxicity. In this study, interaction between ZnO or SiO2 nanoparticles and food ingredients or biological matrices was assessed in terms of changes in their physicochemical properties, in vitro and in vivo solubility, and fluorescence quenching to determine biological fate. Quantitative analysis of saccharides, lipids and minerals which interact with nanoparticles was performed using HPLC, GC-MS and ICP-AES respectively. The results demonstrate that nanoparticles can interact with food components or biological matrices, inducing changes in their physicochemical properties in foods or biological fluids and high fluorescence quenching ratio. Biological fate of nanoparticles was highly dependent on their in vivo dissolution property. Further study is needed to investigate whether these interactions will affect absorption efficiency and potential toxicity as well.

R.9.9
13:30
Authors : Hyeon-Jin Kim, Mi-Ran Go, Song-Hwa Bae, Jin Yu and Soo-Jin Choi
Affiliations : Department of Food Science and Technology, Seoul Women’s University, Republic of Korea

Resume : Silicon dioxide and titanium dioxide nanoparticles have been applied to food industry as an anticaking and food coloring agents, respectively. However, there is little information about their undesirable effects on human health and biokinetic behaviors. In this study, physicochemical properties, intestinal transport mechanism, and biokinetics of food additives silicon dioxide and titanium dioxide nanoparticles were evaluated with respect to particle size (nano versus bulk). We also evaluated the effects of the presence of food ingredients, such as saccharides and proteins, on oral absorption. Biokinetic results demonstrated that silicon dioxide nanoparticles rapidly and largely entered the bloodstream as compared to bulk-sized materials after a single-dose oral administration to rats, while oral absorption efficiency of titanium dioxide was not affected by particle size. Both nanoparticles were determined to be more effectively transcyrosed by microfold (M) cells, present in intestinal epithelium, using in vitro model of human follicle-associated epithelium model. No significant effects of particle size of both materials on tissue distribution and excretion were found. On the other hand, oral absorption of both nanoparticles was extremely low and also highly affected by the presence of food ingredients. These findings will be useful to understand and predict potential toxicity of food additives inorganic nanoparticles.

R.9.10
13:30
Authors : Song-Hwa Bae, Hyeon-Jin Kim, Mi-Ran Go, Jin Yu, Soo-Jin Choi
Affiliations : Department of Food Science and Technology, Seoul Women's University, Republic of Korea

Resume : With increasing attention to healthy foods, nanotechnology have been attempted to develop functional foods and high value agricultural products. Especially, gold nanoparticles (Au-NPs) have shown to have capability to extend shelf-life and enhance sensory characteristics and functionality of some crops, such as rice, apple, and peach. In this study, the toxicity of colloidal Au-NPs and the extract of Au-NPs-treat red ginseng was evaluated in human intestinal INT407 cells and after 14-day repeated oral administration to rat, respectively. As a result, colloidal Au-NPs showed no cytotoxicity in INT-407 cells after 24 h exposure in terms of inhibition of cell proliferation, membrane damage, and generation of reactive oxygen species, although colony forming ability significantly decreased by exposure to Au-NPs for more prolonged time at high concentration. Biokinetic study revealed that extremely small amount of Au-NPs was absorbed into the blood stream and biological fate of Au-NP is primarily in nanoparticulate form at the systemic levels. 14-day repeated oral toxicity study of Au-NPs and the extract of Au-NPs-treated red ginseng demonstrated no significant changes in body weight, mortality, hematological and blood biochemical parameters, and histopathological morphology. Overall results suggest that Au-NPs and Au-NPs-treat red ginseng did not cause severe toxic effects, implying their excellent potential for high value agricultural products.

R.9.11
13:30
Authors : Roik N.V., Belyakova L.A.
Affiliations : Chuiko Institute of Surface Chemistry of NAS of Ukraine, 17 General Naumov Str., Kyiv, 03164, Ukraine

Resume : Drug delivery systems can successfully recognize the diseased cells and liberate biologically active compounds directly to target. In the present work, silica carriers equipped with molecular and supramolecular pH-responsible nanovalves were designed by combination of sol-gel synthesis and selective post-synthetic modification. Mesoporous structure of synthesized materials was characterized by low temperature nitrogen adsorption-desorption, small-angle X-ray diffraction and transmission electron microscopy. Chemical immobilization of N-[N’-(N’-phenyl)-2-aminophenyl]-aminoalkyl groups was confirmed by IR spectral and chemical analysis of surface layer. Protolytic properties of grafted aromatic amino groups were studied by potentiometric titration method. It was found that basicity of aromatic amino groups of MCM-41-type mesoporous silica surface increases in the presence of β-cyclodextrin. Loading and release behavior of silica drug carriers was studied in phosphate buffer solutions with pH = 7.0 and 5.0, correspondingly, using doxorubicin as a test compound. It was shown (by UV spectroscopy measurements) that the loading efficiency of mesoporous materials reaches 59-76 %, whereas cumulative values of doxorubicin released from silicas with surface molecular and supramolecular nanovalves into the phosphate buffer solutions with pH = 5.0 achieve 48% and 51%, respectively. Obtained results demonstrate that aromatic amino groups and surface supramolecular structures localized near by pore openings play essential role in pH controlled liberation of doxorubicin.

R.9.12
13:30
Authors : Adam R. Town, Michael E. Briggs, Marco Giardiello and Tom. O. McDonald
Affiliations : Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, United Kingdom

Resume : Injectable, sustained release drug delivery offers the potential for reducing medical complications by improving patient adherence. [1] Solid drug nanoparticles (SDNs) [2] have the highest drug loading of nanomedicines and offer great potential as reservoirs for long-term drug delivery. However, currently there is only no control of the rate of drug release from such depot sites. To address this issue, we have developed a novel polymer system which entraps the SDNs a polymer gel upon injection. We have shown that thermally-responsive behaviour of poly(N-isopropylacrylamide) nanoparticles can be designed to gel under specific conditions. Heating of the PNIPAM nanoparticles above their lower critical solution temperature to 37°C at physiological ionic strength, resulted in the PNIPAM nanoparticles aggregating into a gel. This gel is capable of entrapping up to 40 % w/w of SDNs. Such nanoparticle/gel composites show controlled drug delivery of the HIV drug lopinavir over periods of time >60 days and that the polymer composition can be used to tune the rate of drug release. These nanoparticle/gel composites will offer the potential for sustained release of dissolved drug molecules from an injected depot in the body. Such drug delivery systems may significantly improve patient outcomes for the treatment of long-term conditions such as HIV. References 1. Hoffman, A. S. J. Control. Release 132, 153?163 (2008) 2. McDonald, T. O. et al. Adv. Healthc. Mater. 3, 400?411 (2014)

R.9.13
13:30
Authors : PhD. Student Suha A A Zwayen
Affiliations : Nanotechnology Drug Delivery Department, School of Pharmacy and Biomedical Science, University of Central Lancashire, Preston- UK.

Resume : Malaria is a global health priority with more than three billion people at risk of acquiring the disease transmitted to humans by the bite of female mosquitoes ?Anopheles gambiae?, one of the most widespread and difficult to control vector. Malaria still falls in the category of neglected disease as it suffers from insufficient research and development in therapy and vaccines worldwide, costing millions of lives, despite the efforts of several non-profit partnership initiatives and the Tropical Diseases Research Programme of the World Health Organization TDR/WHO. Targeting approach for malaria-infected erythrocytes using nanosystems open new doors for the treatment of the disease. The goal of the malaria therapy is targeting the infected RBCs to achieve high intra cellular drug concentration. In order to reach the set goal the carrier system should be able to cross multiple membrane barriers to access the intraparasitic targets. The cell barriers in orderly fashion are the host cell membrane (HCM), the parasitophorous vacuolar membrane (PVM), the parasite plasma membrane (PPM) and food vacuole membrane (FVM) or endoplasmic reticulum membrane (ERM). Upon invasion by malaria parasite, the erythrocyte cell membrane undergoes major changes in the structure, composition and function. Since mature erythrocytes have limited synthetic capabilities, the generation and regulation of pathways responsible for molecular transport in the infected RBC are probably under parasite control. The intraerythrocytic parasite imports nutrients for its development and exports proteins and lipids into the host cell cytoplasm. This transportation occurs through New Permeability Pathways (NPP) in infected RBCs allowing transport of small molecules. Appearance of these membrane pathways increases the permeability of the cell membrane to a wide range of low molecular weight solutes. The existence of interconnected network of tubovesicular membranes (TVM) has shown to be responsible for the import of small molecules whereas secretary cleft and lipid rafts may play a significant role in macromolecular transport in P. falciparum infected human erythrocytes. Certain macromolecules like Dextran, Protein A and IgG2 antibody have shown to have direct access to the parasite. Fluorescent latex beads of size less than 100nm in diameter have shown to enter the infected RBC reaching intracellular parasite. These changes are of interest from the point of view of antimalarial chemotherapy as possible routes for targeting parasiticidal drugs into the intracellular parasite. Thus the aim of the present research work will be to develop and characterise nanoparticulate drug delivery system for targeting preferentially to parasitisiced RBCs (pRBCs) and evaluate antimalarial efficacy for Plasmodium species. The nanoparticles will be fabricated using Quality by Design approach described by ICH guidelines in particle size range of 100-120nm using desolvation followed by high pressure homogenisation. The nanoparticles will be lyophilised for their improved stability and shelf life. The developed nanoparticles will be surface engineered for prolonging their circulation time and specific targeting to pRBCs. Characterization of the nanoparticles will be done for morphology, particle size and polydispersity index, zeta potential, DSC, HPLC, XRD and FTIR analysis, drug entrapment and in-vitro drug release. The nanoparticles will be evaluated for their antimalarial efficacy in-vitro using Plasmodium falciparum. Confocal microscopy will be used to demonstrate the entry of developed nanoparticles inside the pRBC. The toxicity studies will be done to establish the safety nanoparticles.

R.9.14
13:30
Authors : Gabriela Ciobanu (1), Octavian Ciobanu (2)
Affiliations : 1 “Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, Prof. dr. docent Dimitrie Mangeron Rd., no. 63, 700050, Iasi, Romania; 2 “Grigore T. Popa” University of Medicine and Pharmacy, Faculty of Medical Bioengineering, Universitatii Str., no. 16, 700115, Iasi, Romania.

Resume : In this work, we have developed a new chitosan-nanohydroxyapatite biocomposites with biomedical applications such as tissue engineering and drug delivery. The biocomposites were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling, degradation and biomineralization capability. Drug delivery through the biocomposites was examined using Fosamax (alendronate sodium, a bisphosphonate). The results obtained suggest that the developed biocomposites possess the essential requisites for their application in the fields of tissue engineering and drug delivery.

R.9.15
13:30
Authors : Guillaume Thomas1, Thomas Courant1, Julien Boudon1, Mathieu Moreau2, Paul Walker3, Alexandra Oudot4, Franck Denat2, François Brunotte3, Nadine Millot1
Affiliations : 1 ICB UMR 6303 CNRS-Université Bourgogne Franche-Comté, Dijon, France; 2 ICMUB UMR 6302 CNRS-Université Bourgogne Franche-Comté, Dijon, France; 3 Département de Spectroscopie par Résonance Magnétique, CHU Dijon, France; 4 Plateforme d?Imagerie Préclinique, Service de Médecine Nucléaire, Centre Georges François Leclerc, Dijon, France

Resume : SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) are widely used in biomedical applications (hyperthermia, drug delivery and T2 contrast agents for Magnetic Resonance Imaging (MRI)) thanks to their chemical and biological properties [1-3]. This multimodal probe is a great tool for theranostics. For many years, our lab has developed oxide nanoparticles (NPs) with a narrow size distribution by means of a continuous hydrothermal process [4]. These NPs can be coated in situ by organic molecules like catechols, in particular 3,4-dihydroxy-L-phenylalanine (L-DOPA) [4]. This type of ligand leads to an anti-oxidizing effect and an improvement of suspension stability at physiological pH [4,5]. In this study, a multimodal magnetite (Fe3O4) NPs used as contrast agent for MRI/PET (Positron Emission Tomography) double imaging has been developed. This multimodal agent is easily synthesized by the successive adsorption of three nitrodopamine-based PEGs or macrocycle ligands. The grafting of ligands was confirmed by exhaustive characterizations. The imaging agent is stable under physiological conditions and shows no interaction with serum proteins. Yields of radiolabeling indicate an efficient chelation. In vitro, in vivo and biodistribution results on the constituting elements of the final NPs will be presented. Considering these preliminary results, the elaborated nanohybrids appear as promising contrast agents for MRI/PET with a view to cardiovascular diseases imaging. [1] J. Boudon et al., Chem. Commun., 2013, 7394 [2] L. Maurizi et al., Langmuir, 2009, 8857 [3] L. Maurizi et al., J. Biomed. Nanotechnol. 2015, 126 [4] L. Maurizi et al., Chem. Commun., 2011, 11706 [5] G. Thomas et al., RSC Adv., 2015, 78614

R.9.16
13:30
Authors : Fadoua Sallem1-2, Alexis Loiseau1, Adel Megriche2, Mohamed El Maaoui2 and Nadine Millot1
Affiliations : 1) Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303 CNRS – Université de Bourgogne Franche-Comté, 9 Avenue Alain Savary, BP 47870, 21078 Dijon, France; 2) Laboratory of Applied Mineral Chemistry, UR11ES18, Department of chemistry, Faculty of Sciences of Tunis, Tunis El Manar University, Campus universitaire Farhat Hached, 2092-Tunis, Tunisia

Resume : Titanate nanotubes (TNTs) synthesized via hydrothermal process have attracted extensive interest since their first synthesis owing to their special physicochemical properties such as high aspect ratio. So that, they have been used in various applications such as photocatalysis, energy production, medicine (carriers of medicament) [1]. In spite of their special physicochemical properties and their low cytotoxicity [1], titanate nanotubes (TNTs) present some shortcomings which limit their use as biomaterials such as strong aggregation and a poor solubility [2]. To overcome these limits, organic functionalization of TNTs may be a good alternative. This work consists to functionalize TNTs with 3,4- dihydroxycinnamic acid (DHCA), amino acid L-3,4-dihydroxyphenylalanine (L-DOPA), 3-aminopropyltriethoxysilane (APTES), and chitosan in order to make them suitable for a biomedical application. These molecules improve TNTs properties such as long-term stability under physiological conditions (DOPA and DHCA) and good biocompatibility (APTES, chitosan). Experimental conditions (pH, temperature, time reaction, molar ratio…) have been discussed and optimized in order to obtain the highest grafting efficiency for all the studied compounds. The obtained compounds were characterized by a large range of techniques including transmission electron microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), thermal analysis (TGA), IR and UV-visible spectroscopy, and zeta potential measurements. [1] A-L. Papa et al., Nanotox. 2013, 7, 1131 [2] A-L. Papa et al., Dalton Trans 2015, 44, 739

R.9.17
13:30
Authors : S. Sruthi1-2, A. Loiseau1, J. Boudon1, G. Lizard3, P.V. Mohanan2, N. Millot1
Affiliations : 1Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303 CNRS – Université de Bourgogne Franche-Comté, BP 47870, 21 078 Dijon cedex, France; 2Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695012, Kerala, India; 3Laboratoire Bio-PeroxIL, Faculté des Sciences Gabriel, 6 Boulevard Gabriel - 21000 Dijon, France

Resume : Titanate nanotubes (TiONts) and zinc oxide nanoparticles (ZnO NPs) present enormous bio application capabilities. TiONts have already been reported for their application in biosensor, cancer treatment (Mirjolet et al. 2013), bio imaging, bone regeneration and for drug and gene delivery applications (Papa et al. 2013). TiONts possess needle shape morphology with a cavity and open ends. This structure aids in the functionalization and cellular uptake of the TiONts. In the present study cellular interaction of in-house synthesized and characterized TiONts with glial cells were evaluated prior to proposing them as an agent for glioma treatment. These materials were compared for its toxicity, with ZnO NPs known to be toxic to glial cells (Sruthi et al. 2015). In brief, the nanoparticles were synthesized by classical hydrothermal method and the ZnO NPs were synthesised by wet precipitation method. The synthesized particles were characterized by TEM, SEM, XRD, SAED, Zeta potential and surface area measurements, DLS, XPS, IR, and Raman spectroscopies. The particles were analyzed for their biocompatibility and toxicity using glial cell line. MTT assay was carried out to determine the dose response of the particle incubated with the cells. Particle uptake by the cells was determined using TEM and FACS analysis and the cellular vesicles were examined for the presence of particle. The toxicity of nanoparticle is mainly attributed to its ability to generate Reactive Oxygen Species (ROS), measured using DCFH-DA. Cell death induced by the particle and genotoxic potential was studied in detail to better understand the cellular interaction of the particle. The current study will lay a foundation for the safer use of this nanoparticle for the glioma treatment in the future. S. Sruthi et al., Colloid Surface B, 133 (2015) A.-L. Papa et al., Nanotoxicology, 7 (2013) C. Mirjolet et al., Radiother. Oncol., 108 (2013)

R.9.18
13:30
Authors : S.I. Drapak (1), Y.B. Khalavka (2), O.I. Fediv (3), S.V. Gavrylyuk (2), Z.D. Kovalyuk (1)
Affiliations : (1) Frantsevich Institute of Material Sciences Problems, National Academy of Sciences of Ukraine, Chernivtsi Department, 5 Iryna Vilde Str., Chernivtsi, 58001, Ukraine, e-mail: sdrapak@ukr.net; (2) Yuriy Fedkovych Chernivtsi National University, 2 Kotsyubynskii Str., 58012, Chernivtsi, Ukraine; (3) Bukovinian State Medical University, 2 Theatre Sq., 5800, Chernivtsi, Ukraine.

Resume : Gallium selenide (GaSe) belongs to the large class of layered semiconductors. It is a promising material for usage in THz electronics, as the basis of various optoelectronic devices, a matrix for hydrogen storage, substrates in planar nanotechnologies, etc. The technologies of GaSe nanotubes, nanowalls, nanowires, nanoparticles with the thickness of only one layer synthesis exist for today. In this communication we discuss a possibility to use GaSe in medicine. As follow from many investigations, porphyrins stored in tumors transform into strong oxidants under high intensity light illumination and can destroy a cancerous growth in some cases. It is well known that tumor tissues contain an excess of water in comparison to normal ones. It is generally accepted that GaSe is water-insoluble. We have found that a contact of GaSe with water (even if water is in a bound state) under daylight illumination at room temperature results in the dissolution of this semiconducting compound and the formation of selenous and selenic acids. The obtained results allow to consider GaSe nanoparticles as a promising material not only for early diagnosis of tumors but also for their therapy.

R.9.19
13:30
Authors : Young-Rok Kim
Affiliations : Department of Food Science and Biotechnology & Graduate School of Biotechnology, Kyung Hee University, Yongin, Korea

Resume : As one of the most abundant polysaccharides in nature, amylose is a linear homopolymer of glucose linked with ?(1,4) glycosidic bond. Amylose is known as safe natural material and widely used in food, medicine, and chemical industries with its biocompatible and biodegradable properties. Here, we present a novel approach to prepare pure amylose microparticle by enzymatic synthesis and self-assembly process. Iron oxide nanoparticles can spontaneously be incorporated into the amylose microstructure during enzymatic synthesis to form a well-defined spherical particles with superparamagnetic characteristics. The resulting amylose magnetic particle (AMP) was characterized by TEM, SEM, XRD and VSM magnetometer. For the conjugation of specific antibodies to the surface of AMP, we produced a MBP-SPG chimeric protein by fusing two genes that encode these two proteins and expressing it in E. coli. The specific affinity of MBP and SPG toward amylose and Fc domain of antibody, respectively, enabled us to conjugate antibodies to the surface of AMP. We demonstrated the ability of antibody-conjugated AMP to capture target pathogen, E. coli O157:H7. The target bacteria captured on the surface of AMP were easily concentrated by magnet and be subsequently analysed by quantitative real-time PCR. The antibody-conjugated AMPs were shown to capture over 90% of target bacteria and facilitated the detection procedure by effectively isolating and concentrating low number of target pathogen from a clinical samples.

R.9.20
13:30
Authors : Q. Y. Ang, S.C. Low
Affiliations : School of Chemical Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang, Malaysia

Resume : A rational design of molecularly imprinted polymer (MIP) for selective recognition of creatinine (Cre), a final by-product of kidney metabolite, was proposed based on the hybrid computational simulation and experimental investigation. In this work, morphological insight into the nature of Cre recognition during the course of imprinting was described at molecular level. The Cre-MIP was prepared by sol-gel processing using aluminium ion (Al3+) as the cross-linker and tetraethoxysilane (TEOS) as the monomer. Ab initio method was conducted to investigate the interaction energies (?Es) to predict the most possible configurations of Cre-MIP. A higher ?E constitutes to more binding sites formation in the resultant MIP, leading to better binding efficiency. With regards to the optimized formulation of Cre-MIP, the Mulliken charge distribution was studied and correlated to the selectivity coefficients of MIP with respect to the interfering compounds, e.g. creatine (Cr), N-hydroxysuccinimide (N-hyd), 2-pyrrolidinone (2-pyr). The results have come up with a good agreement between theoretical computations and empirical data, which extended the validity of computational screening in MIP systems in an experimental-free approach

R.9.21
13:30
Authors : Sarah Schmidt, Bernd Güttler, Rainer Stosch
Affiliations : Physikalisch-Technische Bundesanstalt Bundesallee 100 38116 Braunschweig Germany

Resume : Raman spectrometry provides a huge variety of applications in biological and biomedical research. Besides characterization of cells and tissue, it allows for identification and quantification of disease related significant Biomarkers present in human body fluids. Quantitative measurements with the aim to ensure metrological traceability can be performed by applying the isotope dilution (ID) principle. This approach, which results in significantly lower uncertainties, requires the determination of an intensity ratio resulting from Raman signals of the natural biomolecule (analyte) and signals from an isotopologue which has a minimal higher molecular weight than its natural form. In combination with surface-enhanced Raman scattering (SERS), biomarkers at their relevant concentration levels can be measured. Here, we report on an approach that aims in combining the accuracy of the ID-principle with the sensitivity and specificity of a SERS-immunoassay. The preparation of the preferably gold nanoparticles involves coating with a Raman reporter molecule (dye) in a natural and isotope-edited form for detection and quantification and the use of suitable antibodies which are targeted against the biomolecule of interest. The specificity of this coherent complex is given by the antibodies which are used. In this manner, a reference procedure for the quantification of ß-Amyloid and tau-protein in cerebrospinal fluid (CSF) as a diagnostic test for Alzheimer disease shall be realized.

R.9.22
13:30
Authors : Francesco Rossi, Nguyen TK Thanh
Affiliations : Francesco Rossi: PhD Student, University College of London, Department of Physics and Astronomy. Nguyen TK Thanh: Professor, FRSC, MInstP, Chair in Nanomaterials, University College of London, Department of Physics and Astronomy.

Resume : The plasmon resonance of gold nanorods (GNR) is able to convert absorbed light in heat, making them promising candidate for hyperthermia study in biological samples. The use of these particles have been limited by the difficulty of obtaining a precise control on the length of the rods and by the necessity of using toxic surfactants as template during the formation of the particles. GNRs have been synthetized using CTAB micelles as template and they have been tuned to desired aspect ratio by varying the concentration and the affinity for gold of the salts in solution. In order to increase the biocompatibility of the nanorods the presence of CTAB on the surface have to be removed. Our procedure offers a reliable and versatile preparation route in order to obtain high control on the aspect ratio of the rods and an efficient method to remove the presence of surfactant from the surface of the rods. The results have been obtained using cycles of ultracentrifugation and redispersion in presence of a polymeric agent. This polymer is able to lightly bind the surface of the nanorods offering a weak stabilization and it can be easily displaced by a stabilizing agent with greater affinity for the surface of the rods. GNRs stabilized with citrate, dodecanthiol and PEG-thiol have been tested for biocompatibility and hyperthermal properties.

R.9.23
13:30
Authors : Filice Marco, Pellico Juan, Lechuga-Vieco Ana Victoria, Bilbao Izaskun, Ruiz-Cabello Jesus, Herranz Fernando
Affiliations : Advanced Imaging Unit (AIU) Spanish National Research Centre for Cardiovascular Disease (CNIC) Melchor Fernández Almagro, 3. 28029, Madrid. Spain

Resume : Due to their unique features, multifunctional magnetic nanoparticles have emerged as key-element to foster the development of a cutting-edge technology such as multimodal imaging (e.g. PET/MRI). To this direction, we developed a novel microwave-based ?one-step? tunable strategy allowing the practical preparation of coated iron oxide magnetic nanoparticles with 68Ga radioisotope directly integrated onto the nanoparticle core. By means of the fine control of different reaction parameters (TºC, coating (dextran or citric acid) and reactant ratio), a highly reproducible set (N=5) of various chelator-free multifunctional radio-MNPs has been achieved in a very fast manner (10 min). Independently of every designed protocol, each produced MNPs set is characterized by possessing very small size (core size from 2 to 4nm; hydrodynamic size from 20 to 85 nm), high radiolabeling yield (>90%) and good T1 values (positive contrast in MRI). After modification of their surface with specific signaling peptides, these multifunctional nano-radioplatforms have been validated for in vivo single and multimodal imaging (PET/MRI) in different mice models. In more details, detection and quantification of neutrophilia, detection of tumor angiogenesis and coronary MRI enhancement have been successfully carried out. In conclusion, a high quality and reproducible single multifunctional nano-radioplatform for in vivo multimodal imaging of different pathological processes has been satisfactorily obtained.

R.9.24
13:30
Authors : Samir A. Belhout, Ji-Yoon Kim, David T. Hinds, Jonathan Coulter, and Susan J. Quinn
Affiliations : Samir A. Belhout - School of Chemistry, University College Dublin, Ireland; Ji-Yoon Kim - School of Chemistry, University College Dublin, Ireland; David T. Hinds - School of Chemistry, University College Dublin, Ireland; Jonathan Coulter, School of Pharmacy, Queens University Belfast, Northern Ireland; Susan J. Quinn - School of Chemistry, University College Dublin, Ireland

Resume : Tailored nanoparticle properties have wide ranging potential in areas of energy conversion, catalysis, diagnostics, sensing, imaging and therapeutics.[1] Hybrid materials comprising supported nanoparticles are advantageous as they are easy to handle and manipulate, and also provide a highly localized concentration of nanoparticles.[2] An eloquent example of their application is the use of supported particles as radiosensitizers in cells.[3,4] For diagnostic and therapeutic applications the support offers additional avenues for targeted delivery in vivo. Though a variety of methodologies exist to prepare robust composites using gels, polymer networks, micelles, microspheres, achieving controlled coating remains a key challenge. In this study the preparation of a variety of composites will be presented together with the methodologies used to quantify the gold loading, as well as the application of these hybrid materials as radiosensitizers with good dose enhancement factors when exposed to radiation. A variety of families were studied, consisting of polystyrene sphere supports (60 nm - 200 nm) with various sized gold nanoparticles (4.5 nm - 26 nm) immobilized. REFERENCES [1] S. Eustis, M. A. el-Sayed, M. Chem. Soc. Rev. 2006, 35, 209?217. [2] J. M. Campelo, D. Luna, R. Luque, José M. Marinas, A. A. Romero ChemSusChem 2009, 2, 18?45. [3] K. T. Butterworth, S. J McMahon, F. J. Currell, K. M Prise Nanoscale, 2012, 4, 4830-8. [4] S. Jain, J. A Coulter, K. T Butterworth, A. R Hounsell, S. J McMahon, W. B Hyland, M. F Muir, G. R Dickson, K. M Prise, F. J Currell, D. G Hirst, J. M O'Sullivan Radiother Oncol., 2014, 110, 342-7.

R.9.25
13:30
Authors : Anil Patel (PhD), Catherine Berry (Principle Investigator)
Affiliations : University of Glasgow; Centre of Cell Engineering; EPSRC; BBSRC

Resume : An estimated 10 million people worldwide are diagnosed with cancer every year, with the World Health Organization (WHO) projecting around 13.1 million cancer- related deaths by the year 2030. Current treatments include surgery, chemotherapy and radiotherapy, however all such treatments suffer unpleasant side effects. To this end, cancer tissue specific hyperthermia is a relatively new technique envisaged by researchers, reliant on the exploitation of cancer cell vulnerabilities to specific temperature profiles (42-45°c). The aim of this study is to assess potential heat delivery to cancer cells using gold nanoparticles (GNPs). GNPs generate heat via surface plasmon resonance when exposed to laser radiation. Two cancer cell lines were adopted for the study, MG63 (osteosarcoma) and MCF-7 (breast cancer), in standard monolayer culture and in multicellular 3D spheroid culture. Two types of GNPs were synthesised, nanorods and nanoprisms. Preliminary experiments verified GNP biocompatibility via the MTT assay and cell-GNP interaction was observed via SEM imaging. GNP uptake into cells was qualified using TEM and quantified using mass spectroscopy analysis. GNPs were then assessed for potential heat generation in cells with laser irradiation. Results demonstrated cell death when exposed to laser/GNPs, but not laser alone, as visualised by a fluorescence live/dead assay. Key genes expressed during cell death (e.g. heat-shock proteins and caspases) are being analysed to determine if necrosis or apoptosis is responsible, using Fluidigm Dymanic Arrays.

R.9.26
13:30
Authors : Mark R. Prestly, Tom O. McDonald
Affiliations : Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, United Kingdom

Resume : Implantable drug delivery systems (IDDS), which deliver a sustained release of a drug over extended periods of time, have been shown to be effective in several therapeutic areas. [1] If a therapeutic regimen requires a patient to take drug doses frequently or over a long time period, adherence will be impacted leading to increased morbidity and mortality. The preparation of poorly water soluble pharmaceuticals as solid drug nanoparticles (SDN) which can be dispersed in water has significant benefits, [2] including increased oral bioavailability, reduced side effects and improved targeting. [3] We are working on the synthesis of charged polymer microparticles which when combined will form a porous hydrogel network which can store and release SDNs. These charged polymer microparticles consist mainly of hydroxyethyl methacrylate (HEMA) or Dextran-HEMA monomers along with ionisable co-monomers. When oppositely charged microspheres are combined in the presence of SDNs a hydrogel microparticle network will be formed and the release of drug containing nanoparticles from this IDDS will be studied. The advantages of such an IDDS is that it combines the sustained long-term drug delivery with the improved targeting provided by nanomedicines. References 1.Hoffman, A.S., J.Contr.Rel., 2008, 132, (3),153; 2.McDonald,T.O. et al., Adv. Healthcare Mater., 2014, 3, 400; 3.McNeil,S.E., WIREs:Nanomed.Nanobiotech., 2009, 1, 264.

R.9.27
13:30
Authors : Antonio Sorarù (a), Loretta L. del Mercato (b), Ilenia Viola (b), Valentina Arima (b), Marcella Bonchio (a), Mauro Carraro (a)
Affiliations : a) University of Padova - Department of Chemical Sciences and ITM-CNR, Via Marzolo 1,35131, Padova, Italy b) NNL, Nanoscience Institute?CNR Via Arnesano, 16, 73100 Lecce, Italy

Resume : The tetraruthenium substituted polyoxometalate [Ru4O4(OH)2(H2O)4(gamma-SiW10O36)2]10- (RuPOM) is a nano-sized bio-mimetic inorganic catalyst. We have investigated its catalase (CAT) and superoxide dismutase (SOD) activity in physiological-like environment, demonstrating its potential as robust artificial antioxidant enzyme, for Reactive Oxygen Species (ROS) scavenging. Owing to its polyanionic charge, RuPOM can be easily integrated into nano/micro carriers, by exploiting Layer-by-Layer (LbL) self-assembly procedures. In particular, it was immobilized within the shell of polyelectrolyte multilayer microcapsules (PMCs) containing a soft fluorescent core. Dioxygen bubbles evolved during H2O2 dismutation were shown to propel the movement of the capsules in a aqueous mixture containing a H2O2 gradient. In addition, as highlighted by using a microfluidic channel, the capsules induce an elastic turbulence of the fluid, depending on the kinetic parameters of H2O2 dismutation.

R.9.28
13:30
Authors : Dirk H. Ortgies, Leonor de la Cueva, Blanca del Rosal, Francisco Sanz-Rodríguez, Nuria Fernández, M. Carmen Iglesias-de la Cruz, Gorka Salas, David Cabrera, Francisco J. Teran, Daniel Jaque, and Emma Martín Rodríguez
Affiliations : Ortgies, D. H.; del Rosal, B.; Jaque, D.; Martín Rodríguez, E. - Fluorescence Imaging Group, Departamento de Física de Materiales, Facultad de Ciencias, Universidad Autónoma de Madrid, C/Francisco Tomás y Valiente 7, Madrid 28049, Spain Sanz-Rodríguez, F. - Fluorescence Imaging Group, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, C/Darwin 2, Madrid 28049, Spain Fernández, N.; Iglesias-de la Cruz, M. C. - Fluorescence Imaging Group, Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Avda. Arzobispo Morcillo 2, Madrid 28029, Spain Ortgies, D. H.; Sanz-Rodríguez, F.; Jaque, D.; Martín Rodríguez, E. - Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Ctra. Colmenar km. 9.100, Madrid 28034, Spain de la Cueva, L.; Cabrera, D.; Salas, G.; Teran, F. J. - iMdea-Nanociencia, Campus Universitario de Cantoblanco, Madrid 28049, Spain Salas, G.; Teran, F. J. - Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, Spain

Resume : Breakthroughs in nanotechnology allow the integration of different nanoparticles single hybrid nanostructures (HNSs), forming multifunctional nanosized sensors with an excellent perspective in the life sciences while small luminescent nanoparticles (LNPs) have brought great advances to the areas of imaging and sensing but most of them use ultraviolet or visible light and are hence limited to cellular studies or topical applications. For in vivo bioimaging LNPs excited by and emitting in the infrared hold more promise because of their ability to penetrate biological tissue.[1] Combining our interest in LNPs that emit IR light between 1000 ? 1350 nm, an area with minimal biological tissue absorption and scattering defined as the 2nd biological windows (II-BW) with the strive for multimodal/multifunctional nanoparticles, we developed HNSs based on poly-lactic-co-glycolic acid (PLGA) that include superparamagnetic iron oxide and quantum dots, which absorb and emit in the II-BW. We demosntrated their ability for in vivo multimodal imaging (MRI and infrared fluorescence) in mice, overcoming the tissue penetration limits of classical visible-light techniques. Additionally, their multifunctionality was studied through the assessment of their applicability as potential magnetic heating agents in hyperthermia treatments.[2] In summary, HNSs including magnetic and luminescent nanoparticles were synthesized and applied to in vivo multimodal bioimaging while also demonstrating their magnetic hyperthermia capability. [1] D. Jaque, B. d. Rosal, E. M. Rodríguez, L. M. Maestro, P. Haro-González, J. G. Solé Nanomedicine 2014, 9, 1047. [2] D. H. Ortgies, L. de la Cueva, B. del Rosal, F. Sanz-Rodríguez, N. Fernández, M. C. Iglesias-de la Cruz, G. Salas, D. Cabrera, F. J. Teran, D. Jaque, E. M. Rodríguez ACS Appl. Mater. Interfaces 2016, DOI: 10.1021/acsami.5b10617.

R.9.29
13:30
Authors : Cornelia Nichita1,2, Georgeta Neagu2, Adriana Balan1 and Ioan Stamatin1
Affiliations : 1University of Bucharest, Faculty of Physics, 3Nano-SAE Research Centre PO Box MG-38, Bucharest-Magurele, Romania 2 National Institute for Chemical-Pharmaceutical Research and Development, 112 VitanStreet, 031299, Bucharest, Romania, e-mail: cornelianichita@yahoo.com

Resume : Non-chemically cross-linked chitosan converted in biogel by sono-chemical synthesis in high density ultrasonic, was evaluated as support for drug delivery aiming to obtain nontoxic functional biopolymer network. The successful crosslinking was performed by OH-radicals generated during cavitation in aqueous solution of acetic acid. The capacity of swelling and pH-responsive, antioxidant activity is estimated for silymarin. In vitro pharmacological tests was performed on 3T3 fibroblasts (ACC 173). The chitosan self -crosslinked network shows a hydrodynamic diameter measured by DLS for chitosan molecules with DDA-80%; a high capacity of swelling up to 96% for silymarin; the antioxidant activity ~ 96% has been measured by chemiluminescence and DPPH methods. Pharmacological evaluation, show significant values for cell viability at application of concentration of 0.1 mg/ mL and 1 mg/ml (96.99% for 0.1 mg/ mL samples and 65.74 - 99.53% for 1 mg/ mL samples). Keywords: drug delivery nano systems, herbal extracts, antioxidant activity, silymarin

R.9.30
13:30
Authors : Tzu-Chun Wang, Chi-Young Lee, Hsin-Tien Chiu
Affiliations : Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30010, Taiwan, R.O.C. Department of Materials Science and Engineering, National Tsing Hua University Hsinchu 30013, Taiwan, R.O.C.

Resume : We electropolymerized polypyrrole thin layer onto Au nanowires via cyclic voltammetry (CV) as molecular imprinted polymer (MIP) biosensor to detect dopamine (DA) and catechol (CA). The Au nanowires/polypyrrole core/shell structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy and linear sweep voltammetry (LSV) was used for sensitivity and selectivity test. Selectivity of MIPs is due to binding sites which are complementary in size and shape to target molecules. Therefore, these sites can recognize targets and rebind them. The DA sensor showed LSV signal intensity at 9.5 μA mM-1 and CA sensor at 10.7 μA mM-1. The determined linear range was 5 x 10-5 - 5 x 10-4 mol L-1 (N=3)

R.9.31
13:30
Authors : Eun-Hee Lee 1, Seung-Woo Lee 2, Ravi F. Saraf 3*
Affiliations : 1 Department of Environmental Science and Engineering, Ewha Womans University, Ewhayeodae-gil Seodaemun-gu, Seoul 120-750, Republic of Korea; 2 Interface Control Research Centre Future Convergence Research Division Korea Institute of Science and Technology (KIST), Hwarang-ro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; 3 Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, USA.

Resume : Early stage of Paramecium bursaria chlorella virus 1 (PBCV-1) infection on Chlorella (green algae) is non-invasively measured using electrochemical field-effect transistor (eFET) in real-time. The eFET made from a network of one-dimensional (1D) Au nanoparticle necklace arrays, which spans over 70 µm, has extreme sensitivity to a single-electron charge at room temperature (RT), resulting in the high specificity and sensitivity of electrophysiological changes of microorganisms. The applicability of the device is demonstrated by measuring the membrane depolarization of the Chlorella and K ion exocytosis from the cells in real-time during the virus infection process. The viral infection is also confirmed by quantitatively measurement of eFET coupled with delivery of viral particles by a scanning probe microscope cantilever.

R.9.32
13:30
Authors : Lucie Ostrovska1,2, Takashi Kanno3, Hiroshi Sugimoto3, Antonin Broz2,4, Jan Valenta5, Anna Fucikova5, Minoru Fujii3, Marie Hubalek Kalbacova1,2
Affiliations : 1 Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic; 2 Institute of Inherited Metabolic Disorders,1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 3 Department of Electrical and Electronic Engineering, Graduate School of Engineering, Kobe, Japan; 4 Institute of Physiology CAS, Prague-Krč, Czech Republic; 5 Faculty of Mathematics and Physics, Prague, Czech Republic

Resume : Silicon is by far the most important semiconductor material enabling high-performance microelectronic and photovoltaic devices. Application spectrum of silicon is further expanding in the field of optoelectronics and photonics. Recently, significant potential of silicon nanocrystals (SiNC) was revealed for their possible application in biology and medicine. They have been studied especially because of their biocompatibility, low toxicity and natural biodegradability. Such characteristics distinguish SiNC from the current semiconductor fluorescence markers called quantum dots which are inappropriate for the application into the living organism due to their potential toxicity. Nowadays, biomedical research concentrates on the possible use of SiNC as tools for bioimaging, biological sensors as well as for drug delivery. Our specially designed SiNC are co-doped with boron and phosphorus and, from the physical point of view, they display exceptional parameters - well defined concentration and crystal size (3-4 nm) in methanol colloid, long lasting dispersion in aqueous solutions, photostability and photoluminescence insensitive to the changes of the environment and to surface modification. Thus these alloy-like SiNC are applicable in biomedicine. First in vitro experiments with human osteoblastic cell line led to the evaluation of the cytotoxicity of different types of SiNC and to the assessement of the highest non-cytotoxic SiNC concentration suitable for their detection in cells using fluorescence microscopy. Two different types of SiNC (3 and 4 nm) were detected in cells at different time points. Results showed how SiNCs are incorporated into the cells over time. Additionally, we proposed possible influence of the presence or absence of serum (fetal bovine or human) in cultivation media on SiNC cytotoxicity and transport into the cells. Finally, we discuss potential of co-doped SiNC in biomedicine.

R.9.33
13:30
Authors : Mathias DOLCI, Xavier CATTOEN, Greg BARBILLON, Sylvie BEGIN-COLIN, Benoît P. PICHON
Affiliations : Student; CNRS researcher; assiocate professor; full professor; assiocate professor

Resume : Nanoparticles assemblies present a great interest for the development of new advanced applications such as magneto-plasmonic sensors. The structuration of magnetic nanoparticles in arrays envisioned to produce ultra-sensitive nanosensors of bio-molecules thanks to collective and synergistic properties. Surface plasmon resonance (SPR) of gold substrates functionalized by self-assembled monolayer (SAM) of organic molecules has been modulated significantly by controlling the assembling of iron oxide nanoparticles as a monolayer with different density[1]. On the other hand, ?click? chemistry has been demonstrated to be very efficient to control the structure of nanoparticle assemblies and so to modulate magnetic collective properties[2, 3]. The assembling process is controlled by specific interactions between functional groups located at the surface of both SAM and nanoparticles. In this study, we take advantage of this approach to prepare biosensors based on magneto-plasmonic properties. Iron oxide nanoparticle monolayers assembled, which still have functional groups, are post-functionalized using ?click? chemistry by biomolecules which acts as detectors. The very well-known biotin/streptavidin couple has been investigated to assess the efficiency of such sensors[3]. The surface of nanoparticle layer is functionalized by biotin groups which enable the detection of streptavidin by bio-conjugation with. The adsorption of streptavidin is demonstrated by monitoring the shift of SPR signal from gold substrate as function of reaction time and streptavidin concentration. [1] Pichon, B. P.; Barbillon, G.; Marie, P.; Pauly, M.; Begin-Colin, S., Nanoscale, (2011) 3, 4696. [2] Toulemon, D.; Pichon, B. P.; Cattoen, X.; Man, M. W.; Begin-Colin, S., Chem Commun (Camb), (2011) 47, 11954. [3] Barbillon, G.; Bijeon, J. L.; Plain, J.; Royer, P., Thin Solid Films, (2009) 517, 2997.

R.9.34
13:30
Authors : Fatimata DEMBELE, Thomas PONS, Alexandra FRAGOLA, Vincent LORIETTE, Mariana TASSO and Nicolas LEQUEUX
Affiliations : Laboratoire de Physique et d'Etude des Matériaux, ESPCI-CNRS-UPMC UMR8213 10 rue Vauquelin, 75005 Paris France

Resume : There are many advantages in applying nanotechnology to molecular diagnostics to improve the simplicity and the sensitivity of the analysis. Semi-conductor nanocrystals or quantum dots (QDs) in particular demonstrate several properties that make them good candidates for biomolecular recognition. These nanocrystals present narrow size-tunable emission spectra and a broad excitation spectrum. In addition, they offer higher photostability and brigthness compared to conventional organic dyes. The objective of this study is to develop a new diagnostic tool based on fluorescent nanobeads containing quantum dots for a fast and single-molecule detection. Our strategy is to self-assemble QDs into clusters of a few hundreds of nanometers in diameter for an even brighter fluorescence and easily detectable analytical signal. In order to protect their colloidal and photo-stability, the clusters need to be covered with ligands such as a polymer or a silica shell. Our work focuses on the formation of monodisperse QD-based superparticles (SPs). In order to obtain very stable SPs, we chose to grow a silica shell on their surface. Biocompatibility is further assured by a new type of polymer-silica hybrid presenting a zwitterionic chain for water solubility and reactive functions for conjugation with biomolecules. Preliminary results have shown that we can integrate the SPs into a microfluidic system for an efficient single-particle counting.

R.9.35
13:30
Authors : Fabrizio Bertorelle, Marcella Pinto, Lucio Litti, Vincenzo Amendola, Giulio Fracasso, Moreno Meneghetti
Affiliations : Fabrizio Bertorelle, University of Padova, Department of Chemical Sciences; Marcella Pinto, University of Verona, Department of Medicine; Lucio Litti, University of Padova, Department of Chemical Sciences; Vincenzo Amendola, University of Padova, Department of Chemical Sciences; Giulio Fracasso, University of Verona, Department of Medicine; Moreno Meneghetti, University of Padova, Department of Chemical Sciences;

Resume : Nanomedicine is one of the most interesting field of application for nanoparticles (NP). In cancer research, many scientists are currently focusing on building multi-purpose nano or micro systems, often obtained by combining NPs with different properties like gold and iron oxide NPs. Gold NPs are of interest in nanomedicine because of their biocompatibility, easy functionalization and optical properties which make them a powerful cells detection tool using, for example, SERS spectroscopy and for hyperthermal treatment of cancer cells. Iron oxide NPs in particular those made of magnetite, can be used for cell sorting exploiting their magnetic properties. We report the synthesis, by using NPs obtained by Laser ablation Synthesis in Solvents, of core-shell-satellite (CSS) sub-micron systems made of an iron oxide NPs core, dye-doped silica shell and AuNPs as satellite decoration. CSS have been fully characterized and show high SERS activity. They are functionalized with an antibody specific for PSMA antigen overexpressed by prostatic cancer cells. We show that antibody functionalized CSS can be efficiently used in the selective immunomagnetic sorting of prostatic cancer cells and, coupling immunomagnetic sorting with single-cell SERS analysis, a reduction of false positive arising from immunomagnetic sorting procedure is obtained. We also show application of CSS in photothermal treatment of prostatic cancer cells using a continuous laser at 647 nm.

R.9.36
13:30
Authors : F. Pappa, V. Karagkiozaki, S. Moya, Elena Rojas Darceles, J. Llop, Eleftheria Diamanti, D. Arvaniti, S. Logothetidis
Affiliations : Nanomedicine Group, Lab for “Thin Films- Nanobiomaterials, Nanosystems & Nanometrology”, Department of Physics, Aristotle University of Thessaloniki, Greece ; Soft Matter Nanotechnology Sector, Center for Cooperative Research in Biomaterials (CIC-biomaGUNE), San Sebastian, Spain ; Radiochemistry & Nuclear Imaging Sector, Center for Cooperative Research in Biomaterials (CIC-biomaGUNE), San Sebastian, Spain ; BL NanoBiomed P.C, 145 Vasilisis Olgas, 54645, Thessaloniki, Greece

Resume : Atherosclerosis is a chronic disease characterized by the formation of plaque in regions of arteries. Current imaging techniques lack specificity for the plaques and consequently, new selective contrast agent is necessary for accurate imaging of plaque. Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are appealing Drug Delivery Vectors, since they have the ability to be surface engineered in order to increase the body circulation, direct to specific organs or uptake via targeted cells. Since drug delivery reach the cell interior, is fundamental to understand the uptake of the NPs into cells, quantify it and determine the localization intracellular. In this study, we proceed towards the synthesis of PLGA NPs with encapsulated iron oxide NPs, labelled with quantum dots in the particle core for targeting atherosclerotic lesions. PLGA NPs were loaded with rhodamine 6G, an FDA-approved fluorescent agent and used for intracellular localization studies, applying flow cytometry (FACS) and Confocal Scanning Laser Microscopy (CLSM). Studies of PLGA NPs biodistribution with different surface functionalization, took place, allows us to quantify the amount of NPs per organ and the distribution patterns after intravenous delivery. Cytotoxicity studies with hepatocytes further reinforced the ability of NPs to enhance cellular uptake using FACS-CLSM analysis for cellular localization and quantification. Radiolabelled PLGA NPs are appeared to be an excellent biocompatible model for the evaluation of targeting capacity of nanocarriers, with unique biodistribution, cellular uptake and targeting properties, thus to enhance a prototype platform for drug delivery system, especially for cardiovascular diseases.

R.9.37
13:30
Authors : Katarzyna Grochowska1, Katarzyna Siuzdak1, Michał Sokołowski2, Mariusz Szkoda3, Jakub Karczewski2 , Gerard Śliwiński1
Affiliations : 1Centre for Plasma and Laser Engineering,The Szewalski Institute of Fluid-Flow Machinery, Polish Academy of Science, Fiszera 14, 80-231 Gdansk, Poland; 2 Faculty of Applied Physics and Mathematics, Gdańsk University of Technology, Narutowicza 11/12 St., 80-233 Gdańsk, Poland; 3 Department of Chemistry and Technology of Functional Materials, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland

Resume : Recently, metal nanostructures are frequently considered for highly sensitive detectors that show potential in biochemistry and medical diagnostics. In this work we report on preparation and characteristics of ultrathin (5-10 nm) Au films deposited onto highly ordered structured titanium templates for SERS (Surface Enhanced Raman Spectroscopy) and electrochemistry applications. The templates are formed by chemical etching of TiO2 nanotubes out of titanium substrate. The surface of the obtained material perfectly maps the bottom layer of the nanotubes and consists of a uniformly distributed dimples with diameter in the range of 30-100 nm. For the structures covered with ultra thin Au films the measured average SERS signal is markedly higher than observed for bare Ti templates. This is due to strong electromagnetic field in the vicinity of the film discontinuities. The electrochemical response of the prepared Au/Ti substrates studied in the presence of glucose solution shows that the current registered at the oxidation peak rises with the increasing glucose concentration on the contrary to bare Ti for which no activity can be observed. The effect depends linearly on glucose concentrations in the range of 0.1 - 40 mM that covers the physiological detection needs regarding the blood sugar. KG and KS acknowledge the National Science Centre of Poland for financial support via grants 2012/07/N/ST5/02139 and 2012/07/D/ST5/02269.

R.9.38
13:30
Authors : Yekta Arya ÖLÇER, Merve DEM?RKURT AKBAL, Esen Z?YANAK, Ali ÇA?IR, Mustafa M. DEM?R,Ahmet E. ERO?LU
Affiliations : Yekta Arya ÖLÇER-Department of Chemistry, ?zmir Institute of Technology, TURKEY; Merve DEM?RKURT AKBAL-Department of Chemistry, ?zmir Institute of Technology, TURKEY; Esen Z?YANAK-Department of Chemistry, ?zmir Institute of Technology, TURKEY; Ali ÇA?IR-Department of Chemistry, ?zmir Institute of Technology, TURKEY; Mustafa M.DEM?R-Department of Materials Science and Engineering, ?zmir Institute of Technology, TURKEY; Ahmet E. ERO?LU-Department of Chemistry, ?zmir Institute of Technology, TURKEY;

Resume : MIPs are new types of sorbents that can be used for specific recognition of substances. Specificity is achieved by addition of template molecule into reaction medium during polymerization. After washing steps template is removed and specific binding sites are created. The polymer can be synthesized with high yield in a short time and costs less than other methods. Endocrine disrupting compounds (EDCs) are both man-made and natural exogenous substances which cause some disorders in human body by interfering normal hormone working principle. Ibuprofen is a non-steroidal anti-inflammatory drug that we all use in our daily-life. It causes congenital cryptorchidism (deficiency of one or both testicles) to male-child of impregnate by interfering in testis development, which causes testicular cancer in the later life of descendant. For the determination of ibuprofen in water samples poly(MAA-co-TRIM)?s were designed and synthesized in different physical morphologies by changing only the solvent amount of reaction medium. These special polymers were used as sorbent in batch-type solid phase extraction (SPE) and specificity was compared with other structurally related compounds. Depending on morphology, these polymers can be filled into the cartridges either directly or after preparation of an electrospun membrane. These applications are still being tried by our research group to have better results.

R.9.39
13:30
Authors : Miguel Centelles, Michael Wright, Wady Gedroyc, Maya Thanou
Affiliations : Miguel Centelles; Michael Wright; Maya Thanou Institute of Pharmaceutical Science, King?s College London, London, UK Wady Gedroyc Department of Experimental Medicine, Imperial College London, London, UK

Resume : Localised drug delivery to tumours may be applied by the use of a blood compatible nanosized carrier agent able to respond to an external stimulus (such as a temperature increase) with a ?triggered? drug release. Conventional thermosenstive liposomes (TSLs) or similar delivery systems lack the labels for in vivo tracking or tumour imaging and hence the ability to assess the optimal trigger time post administration. Here we discuss a dual labelled thermosensitive liposomal delivery system for localised delivery by Focussed Ultrasound (FUS) assisted mild hyperthermia. In addition to labelling for MRI, we introduced a Near Infrared fluorescence (NIRF) label which greatly assisted in the near real time tracking of the carrier in our murine xenograft cancer model. This in turn allowed for optimisation of the FUS conditions and timings, allowing for triggered-release and functional delivery of the therapeutic drugs to the tumours. NIRF allowed for high sensitivity imaging with little intrinsic tissue background fluorescence and good transmission & tissue scattering characteristics compared to visible region fluorophores. We synthesised these labels as lipid attached conjugates to ensure specific and lasting labelling of the carrier liposomes. MRI contrast enhancement ability and NIRF signals were assessed in vitro and in vivo. Nanoparticle kinetics in murine tumours were assessed with optical imaging and at defined time intervals post i.v. injection, FUS was applied to induce a small increase in temperature to 42-43°C for 3-5 min. Imaging revealed both dramatic nanoparticles accumulation (5-10 fold) and drug release immediately after induced hyperthermia and only in the FUS treated tumour. Significant tumour growth inhibition was observed for the FUS treated tumours compared to those that were treated only with the drug nanoparticles. The applications of such multifunctional ?nanotheranostics? with short, mild hyperthermia could have a transformative effect on cancer chemotherapy.

R.9.40
13:30
Authors : Bo?i? Mojca1, Bra?i? Matej1, Doris Tkau?i?1, Silvo Hribernik1, Manja Kure?i?1, Kargl Rupert1, Spirk Stefan1,2, Mohan Tamilselvan3, Stana-Kleinschek Karin1
Affiliations : 1University of Maribor, Institute for Engineering Materials and Design, Smetanova ulica 17, SI-2000 Maribor, Slovenia 2Graz University of Technology, Institute for Chemistry and Technology of Materials, Stremayrgasse 9, 8010 Graz, Austria 3University of Graz, Institute for Chemistry, Heinrichstrasse 28, 8010 Graz, Austria

Resume : Polysaccharide-based nanoparticles exhibit a great potential as holders for imaging and drug agents because of their intrinsic physicochemical properties being biocompatible and biodegradable. Moreover, they are highly stable, safe, non-toxic, hydrophilic and offer a large variety of functional groups, degree of branching (linear to highly branched) and molecular weight (low to high). Thus, they have a wide variety of composition and properties that cannot be replicated in a chemical laboratory, and the ease of their production makes various polysaccharides cheaper than synthetic polymers. Therefore, the use of polysaccharides as biomaterials is quite promising for biomedical applications. In this work, we will discuss about polysaccharides being a key component in the development of contrast agents for the new magnetic resonance imaging technologies. In this context, different processing strategies for synthesizing different polysaccharide-based composite nanoparticles will be presented. Acknowledgment: This research is supported by the H2020-EU.1.2.1.-founded project ?CONQUER: Contrast by quadrupole enhanced relexation?, Project reference 665172

R.9.41
13:30
Authors : Aeju Lee; Miguel Ferreira; Claudia De Mei; Federica Piccardi; Tiziano Bandiera, Paolo Decuzzi
Affiliations : Laboratory of Nanotechnology for Precision Medicine Fondazione Istituto Italiano di Tecnologia (IIT) via Morego 30, Genova 16163, Italy

Resume : Nanoparticles only can be loaded with therapeutic and imaging agents enabling de facto combination therapy and multimodal imaging. In this work, theranostic polymeric nanoconstructs (TPNs) are realized with a core of poly(lactic-co-glycolic acid) (PLGA) stabilized by a lipid monolayer decorated with polypropylene glycol chains (PEG2000) resulting in ~ 200 nm spheres. TPNs are loaded with potent anti-cancer (docetaxel - DTXL) and anti-inflammatory (diclofenac - DICL) molecules for the treatment of brain tumors. The lipid monolayer is further labeled with near infra-red dye (Cy5) and gadolinium-based macromolecules (Gd-DOTA) for biodistribution analysis and therapy follow-up. In vitro, DTXL:DICL TPNs induce tumor cell death two times more efficiently than DTXL-only TPNs, achieving an IC50 of 90.5 nM at 72h on U87-MG cells. In mice bearing glioblastoma multiforme tumors, TPNs demonstrate the highest efficacy: at 70 days post treatment, survival rates are 70%, 40% and 0% for mice treated with DTXL:DICL TPNs; DTXL-only TPNs and free DTXL, respectively. TPNs accumulation within malignant masses of different sizes, namely of ~ 300, 600 and 1,000 mg, is studied via both fluorescent optical imaging (IVIS Spectrum) and elemental analysis for gadolinium via inductively coupled plasma mass spectroscopy (ICP-MS). Longitudinal relaxivities as high as 60 (mM·s)-1 are documented at 1.41T resulting in significant contrast enhancement in 3T clinical Magnetic Resonance Imaging (MRI) scanners.

R.9.42
13:30
Authors : Ivan Stijepovi?, Marija Milanovi?, Milana Orelj, Vladimir Srdi?
Affiliations : University of Novi Sad, Faculty of Technology Novi Sad, Department of Materials Engineering, Novi Sad, Serbia

Resume : Magnetic nanoparticles consisting of nickel and zinc ferrite are synthesised using co-precipitation method. Nickel ferrite was firstly synthesised as the core particle and stabilised using citric acid and ultrasound agitation. In the second step, these stabilized non-agglomerated particles were used as seeds for the synthesis of core/shell nanoparticles with zinc ferrite as the shell layer. Finally, core/shell particles were stabilized using citric acid and coated with silica layer using tetraethyl orthosilicate (TEOS) in Stöber process. The size and zeta potential of the particles after each synthesis step were monitored using dynamic light spectroscopy (DLS). As synthesised particles were characterized using XRD, SEM, TEM and Raman spectroscopy.

R.9.43
13:30
Authors : Marija Milanović, Ivan Stijepović, Milana Orelj, Vladimir V. Srdić
Affiliations : University of Novi Sad, Faculty of Technology Novi Sad, Department of Materials Engineering, Novi Sad, Serbia

Resume : Magnetic nanoparticles have growing uses in biotechnology and medicine owing to their suitable magnetic properties and appropriate particle sizes. However, due to the low biocompatibility and low dispersion in water solutions, nanoparticles used for biomedical applications require surface treatment. In this work, we have synthesized zinc ferrite nanoparticles by co-precipitation method. Stabilization of magnetic nanoparticles in water is achieved by citric acid as carboxylate-stabilizing agent, biocompatible polymer such as PEG and tetramethyl ammonium hydroxide, TMAOH. The influence of the appropriate stabilizing agents used for surface modification and functionalization of colloids is investigated in terms of the size effect and structural changes by means of DLS, XRD and Raman techniques. Zeta-potential of the synthesized nanoparticles is measured in order to determine their colloidal stability and choose the most appropriate surface modifier.

R.9.44
13:30
Authors : Andrea Borgogno*, Devid Maniglio, Salvatore Iannotta, Tullio Toccoli.
Affiliations : IMEM-CNR Via alla Cascata 56/C, Povo - 38123 Trento; Department of Industrial Engineering, BIOtech Research Center Via delle Regole 101, Mattarello - 38123 Trento ; IMEM-CNR Parco Area delle Scienze 37/A - 43124 Parma, Italy; IMEM-CNR Via alla Cascata 56/C, Povo - 38123 Trento

Resume : Prostate cancer is the second cause of cancer in male population, with the risk of cancer developing typically increasing with age and with familiarity. Early stage detection is crucial for a positive prognosis of the disease when it is still localized within the capsule, before its metastatic transformation. The development of novel and non-invasive approaches for the detection and control of prostate cancer progression is increasing in importance because they could give the possibility of a wide population screening. Nowadays non-invasive detection methods are mainly based of the detection of specific tumor markers inside urine, but unfortunately they are neither enough sensitive, neither enough specific. Prostate-specific antigen (PSA) is an FDA approved marker for prostate cancer screening in USA. Levels between 4 and 10 ng/ml in the blood are considered to be suspicious and prostate biopsy is performed to confirm diagnosis. Laboratory techniques for PSA detection are often expensive, time consuming and they require specialized technicians. In our laboratory, we are developing an Organic electrochemical transistor (OECT) based on PSA antigen incorporated in a PEDOT:PPS conductive polymer for PSA recognition in the urine. This OECT should detect PSA level around 4 ng/ml or lower, it is reusable, economic, non-invasive and easy to use thanks to the embedded electronics. Thus, when optimized, it can be a valuable candidate as a tool for extensive prostate cancer screening.

R.9.46
13:30
Authors : M. A. Ait Kerroum1, A. Essyed1, K. Lasri2, K. Elmaalam2, M. Benali2, O. Mounkachi2, M. Hamdoun2 , A. Benyoussef1,2 and M. Benaissa1.
Affiliations : 1 L.M.P.H.E, Department of physics, Faculty of Sciences, University Mohammed V, Rabat, Morocco; 2 Institute of Nanomaterials and Nanotechnology, MASCIR, Rabat, Morocco

Resume : In the present work, we have synthesized Fe3O4 magnetite ferrite nanoparticles using coprecipitation method, in this study we have controlled the PH of the reaction as it is an important parameter during synthesis. XRD pattern of the obtained black powder shows the presence of the intence peak corresponding to (311) crystallographic orientation of the spinel phase of Fe3O4 magnetite nanoparticle. The mean size of the nanoparticles determined using the Scherrer formula, was in the order of 11nm, which is close to the value measured from Transmission Electron Microscopy which was found in order of 12nm. Magnetic properties of the obtained nanoparticles were determined from the hysteresis loop of magnetization vs the field, which shows a behavior of superparamagnetic nanoparticles which are a good candidate for nanomedicine.

R.9.47
13:30
Authors : Magali Lavenas, Irene Tagliaro, Hervé Seznec, Joao Rocha, Luis Carlos, Marie-Hélène Delville
Affiliations : CNRS, Université de Bordeaux, ICMCB, Pessac, France & Universidade de Aveiro, CICECO, Aveiro, Portugal; Universita degli studi di milano-bicocca, Milan, Italy; CNRS, Université de Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France; Universidade de Aveiro, CICECO, Aveiro, Portugal; Universidade de Aveiro, CICECO, Aveiro, Portugal; CNRS, Université de Bordeaux, ICMCB, Pessac, France

Resume : Cancer is the main cause of mortality in the world. It is crucial to be able to design and, most importantly quantify an efficient therapeutic approach based on multimodal nanoparticles (NPs). Inorganic NPs based on metal oxides (e.g. TiO2 and Hf02) exhibiting several functionalities allowing their localization using various techniques (MRI, luminescence) as well as their quantification (IAB). When these metal oxides are bombarded with ionizing radiation, very large numbers of electrons are generated, considerably amplifying the lethal dose of energy in a tumor. The efficacy of the radiotherapy is thus multiplied, while the dose of irradiation impinging healthy tissues remains low. Two mechanisms may be involved, radioenhancement or radiosensitizer effect. In this context, NPs should be designed with several functionalities such as the ability to cross biological barriers as well as their non-toxicity for the humans. Moreover, it is important to be able to detect them in the human body, especially in the tumor target, via their magnetic or luminescence properties. For this purpose, rare-earth elements are inserted in the metal oxide matrices. As the lethal temperature for healthy and tumor cells differs, it is also important to ascertain the temperature of the cells during ionizing radiation treatment. This may be achieved based on the light emission of suitable pairs of rare-earth elements.

R.9.48
13:30
Authors : Marianna Mamusa, Francesco Barbero, Angels Ruyra Ripoll, Leopoldo Sitia, Kostas Hatzixanthis, Christopher Morris, Debora Berti
Affiliations : Department of Chemistry ?Ugo Schiff? and CSGI, University of Florence, Italy; Nanovector s.r.l., Turin, Italy; School of Biological Sciences, University of East Anglia, Norwich, UK; Norwich Medical School, University of East Anglia, Norwich, UK; School of Pharmacy, University of East Anglia, Norwich, UK; School of Pharmacy, University of East Anglia, Norwich, UK; Department of Chemistry ?Ugo Schiff? and CSGI, University of Florence, Italy

Resume : Microbial resistance to antibiotics has grown over the last few decades into a serious global threat, which must be tackled with innovative therapeutics. We propose to address it by coupling the action of a strong antibacterial, the bolaform cationic surfactant [12-bis-THA]Cl2, with specifically engineered oligonucleotides (TFDs, Transcription Factor Decoys) that can block essential genomic targets in bacteria. Preliminary tests on [12-bis-THA] /TFD nanoplexes have proven antibacterial activity in vivo against Clostridium difficile and MRSA. In order to improve the bioavailability and antibacterial activity of the [12-bis-THA]Cl2/TFD complex, we incorporated it in fusogenic liposomal carriers with controlled composition and morphology. We investigate the effect of the inclusion of the bolaamphiphile in the lipid bilayer and optimize the encapsulation of the oligonucleotide. We characterize the structure of the liposomes by means of dynamic light scattering (DLS), Zeta potential measurements, small-angle x-ray scattering (SAXS), cryogenic electron microscopy (cryo-TEM), UV-Vis absorption and fluorescence spectroscopy. The antibacterial activity and cytotoxicity of these delivery systems are evaluated with in vitro assays, while confocal microscopy experiments on fluorescently labelled samples allow us to assess the delivery of the TFD into model bacterial systems.

R.9.49
13:30
Authors : Zi Hong Mok, Maya Thanou, Van Thompson
Affiliations : Institute of Pharmaceutical Science, King's College London; Institute of Pharmaceutical Science, King's College London; Dental Institute, King's College London

Resume : Background Calcium phosphate nanoparticles (CPNPs) can be used for applications in dental/medical treatments as they are biocompatible, biodegradable and their synthesis can be controlled. Here, we describe the preparation of CPNPs to be used for diffusion studies in hard tissues. We used near-infrared dye, Indocyanine Green (ICG) encapsulated within the nanostructure as a label for the detection of their diffusion through defective calcium phosphate substrates. Methods CPNPs were synthesised with co-precipitation of calcium chloride and sodium phosphate, in a solution of ICG for entrapment. Sodium citrate was then added as a capping agent. Their physicochemical properties, including particle size, zeta potential, morphology and the entrapment efficiency of ICG were characterised. Enamel slabs were then prepared and decalcified to simulate carious lesion. The ability of CPNPs to penetrate carious lesion was examined by staining the porous enamel with the nanoparticles. Results CPNPs were successfully made with an average particle size of 76 ± 14 nm using 300 mM citrate. They had an average zeta potential of – 21 ± 1.1 mV. The entrapment efficiency of ICG was 17%. Spherical and rice-shaped nanoparticles were observed under the AFM. Finally, selective accumulation of calcium phosphate nanoparticles on the decalcified areas of the teeth was observed using near-infrared imaging. At a longer contact period, more CPNPs had accumulated in the porous apatite based substrate, exhibited by a brighter fluorescence on the decalcified area. Conclusion CPNPs doped with ICG showed clear potential to detect and treat defects in hard tissues. For the next stage, we will find out the depth and time dependency of nanoparticle penetration into lesions.

R.9.50
13:30
Authors : S. Mirabella1, K. O. Iwu1, A. Lombardo2, S. Petralia3, E. Castagna3, S. Scirè2, S. Conoci3
Affiliations : 1. MATIS CNR-IMM and Dipartimento di Fisica e Astronomia, Università di Catania, via S. So?a 64, 95123 Catania, Italy 2. Dipartimento di Scienze Chimiche, Università di Catania, via S. So?a 64, 95123 Catania, Italy 3. STMicroelectronics Stradale Primosole 95121 Catania ? Italy

Resume : Non-enzymatic glucose sensing is based on the direct catalytic oxidation of glucose and typically allows very high sensitivity at the expense of high fabrication cost, low selectivity and poor stability. Here we report on a novel NiO nanostructure fabricated by low-cost methods and successfully applied for non-enzymatic glucose sensing [1]. A Ni nanofoam (surface area of 25 m2/g) is obtained by room-temperature chemical bath deposition followed by 350 °C annealing in reducing ambient. To activate glucose detection a catalytic layer of Ni(OH)2/NiOOH is formed onto the nanofoam by cyclic voltammetry (CV). Two glucose sensor electrodes, on flexible and on rigid substrate, were fabricated, both showing sensitivity in the range of 1.5-3 mA/cm2mM, linear range of 0.01?0.7 mM, limit of detection (LOD) of 5 uM, resistance to chloride poisoning and excellent long-term stability (4% decrease in sensitivity after 64 days) and selectivity in the presence of common interfering species. Then, a full device was realized with a miniaturized electrochemical cell, based on a silicon chip with planar microelectrodes, connected to a PCB board (for the electrical driving and reading) and containing also a resistor for sensing test at high temperature. The sensing electrode was based on Ni oxy-hydroxide and glucose testing was performed with NaOH or PBS electrolytes. The device sensitivity decreases with decreasing the electrolyte pH, with still some activity also at the physiological pH of 7.4. [1] Iwu et al., Sensors and Actuators B 224 (2016) 764?771

R.9.51
13:30
Authors : S. Soltani(1), M. Bouzidi(1), A. Toure (1), M. Gerhard (2), I. Halidou (1), Z. Chine (1), B. EL Jani (1), M. K. Shakfa (2)
Affiliations : (1) Unité de recherche sur les Hétéro-Epitaxies et Applications (URHEA), 5000 Monastir, Tunisia (2) Department of Physics and Material Sciences Center, Philipps-University of Marburg, Renthof 5, 35032 Marburg, Germany.

Resume : GaN and related alloys such as AlGaN have attracted a great deal of attention due to their potential for wide-band gap optoelectronic and medical diagnostics applications. In the present work, AlGaN/GaN epitaxial films have been grown on SiN surface-treated sapphire substrate by metal organic vapor phase epitaxy (MOVPE) under atmospheric-pressure. The Al content in the studied samples is varied between 3% and 15% though the change of the flow rate of trimethylaluminum (TMA) from 12 µmol/min to 32 µmol/min. The optical properties and carrier dynamics of the AlGaN/GaN epitaxial films are investigated by means of time-resolved Photoluminescence (TR-PL). Low temperature measurements show that the PL emission peak broadens and shifts to higher energies when the TMA flow rate is increased. Simultaneously, the PL decay time increases with increasing Al contents in the studied films. These observations can be attributed to the carrier localization effects in band tail states due to compositional fluctuations in the AlGaN layers. Remarkably, the PL spectrum of the epitaxial film with a relatively high Al content of 15 % reveals several peaks. In order to find out about the origin of these features, temperature-dependent PL measurements are performed in the range from 25 K to 300 K. Keywords: AlGaN, Metal organic vapor phase epitaxy, Photoluminescence, time-resolved photoluminescence.

R.9.52
13:30
Authors : He Huang, Razwan Baber, Hendrik Du Toit, Ivan Parkin, Asterios Gavriilidis
Affiliations : Department of Chemical Engineering, University College London

Resume : The Turkevich method is widely used to synthesize charge stabilised gold nanoparticles (Au NPs) from tetrachloroauric acid by reduction with sodium citrate. The low toxicity and ease at which such Au NPs can be funtionalised have made them very popular for biological applications. However this method is typically limited to producing larger Au NPs in excess of 10 nm. In order to achieve Au NPs which are 5 nm or less, other techniques are typically adopted which rely on the use of powerful surfactants or capping agents to limit particle growth. These particles in turn have more limited applications since the removal of the capping agent is not easily achieved. In our study, the effect of circular capillary microreactor on the size of Au NPs prepared by classic citrate synthesis method has been investigated. Since it is known that microreactor enhances both mass and heat transfer, a faster nucleation rate was expected, which would in turn lead to smaller particle sizes. By studying the effect of different parameters (temperature, initial pH and concentration of precursor and microreactor inner diameter), we have been able to produce Au NPs with mean sizes as low as 3 nm. There is still potential to improve on this result, as more parameters such as microreactor material, mixing method and residence time distribution will be studied in the future.

R.9.53
13:30
Authors : < p>Roxana Jijie,< sup>1,2< /sup> Tetiana Dumych,< sup>3< /sup> Kostiantyn Turcheniuk,< sup>1< /sup> Charles-Henri Hage,< sup>4< /sup> Laurent Helio,< sup>4< /sup> Nicoleta Dumitrascu,< sup>2< /sup> Julie Boukaert,< sup>3< /sup> Rabah Boukherroub< sup>1< /sup> and Sabine Szunerits< sup>1< /sup>< /p>
Affiliations : < p>< sup>1< /sup> Institut d?Electronique, de Microélectronique et de Nanotechnologie (IEMN), UMR CNRS8520, Université Lille 1, Avenue Poincaré-BP 60069, 59652 Villeneuve d?Ascq, France < p>< sup>2< /sup> Iasi Plasma Advanced Research Center (IPARC), Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bd. Carol I No. 11, Iasi 700506, Romania < p>< sup>3< /sup> Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université Lille 1, CNRS UMR 8576, 59655 Villeneuve d'Ascq, France < p>< sup>4< /sup> Laboratoire de Physique des Maser, Atomes et Molécules (PhLAM), Université Lille 1, CNRS UMR 8523, 59655 Villeneuve d?Ascq, France< /p>

Resume : < p align="justify">The increase of multidrug-resistant bacteria infections represents an important bio-medical problem that requires the development of new antibacterial agents for which pathogens will not be able to develop resistance. The photodynamic (PDT) and/or photothermal (PTT) therapy can be considered as a viable alternative to conventional antibiotic therapies, which are becoming less efficient for the inactivation of microorganisms. PDT employs a photosensitizer (PS) molecule to induce irreversible cell damage upon laser irradiation at a specific wavelength. Near infrared (NIR) excitation light in the range of 700 to 1000 nm is of particular interest, because absorption of NIR photons in biological tissues is minimal and the penetration depth is optimal. In this study, we demonstrate that NIR plasmonic nanostructures, composed of silica coated gold nanorods with embedded indocyanine green (Au NRs@SiO< sub>2< /sub>-ICG) exhibit no cytotoxicity to cells and high capacity to inactivate a virulent strain of < i>Escherichia coli (E. coli)< /i> associated with Crohn?s disease under 810 nm pulsed-mode laser irradiation.< /p>

R.9.54
13:30
Authors : A. Mesaros1, L. Mirea-Popa2, L. Perju-Dumbrava2,O. Pop3, Z. Diaconeasa3, E. Ware4, F. Goga5, C. Socaciu3
Affiliations : 1Technical University of Cluj-Napoca, Superconductivity, Spitronic and Surface Science Center – C4S, Cluj-Napoca, Romania 2University of Medicine and Pharmacy, Department of Clinical Neurosciences, Cluj-Napoca, Romania 3Faculty of Food Science and Technology, University of Agricultural Science and Veterinary Medicine Cluj-Napoca, Cluj-Napoca, Romania 4Imperial College London, Exhibition Road, South Kensington, London SW72AZ, United Kingdom 5Babes-Bolyai University, Faculty of Chemistry and Chemical Engineering, 11 Arany Janos Street, Cluj-Napoca, Romania

Resume : Ceria nanoparticles have been successfully synthesized using a new facile and eco-friendly sol-gel method. This approach is based on the thermal decomposition of ceric ammonium nitrate Ce(NH4)2(NO3)6 in the presence of a sucrose-pectin mixture. The chemical nature, structure and morphology of the CeO2 nanoparticles have been investigated by FT-IR, XPS, XRD and TEM. The XRD investigations reveal the formation of the fluorite crystal structure, while the TEM images show the formation of spherical nanoparticles with an average particle size range between 5 to 10 nm. Nanoceria switches between Ce4+ and Ce3+ states creating oxygen vacancies and this capability is similar to that of biological antioxidants. Thus, the antibacterial effect of the nanoparticles against four pathogenic bacteria: Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, Bacillus cereus has been studied. More over, the cytotoxic effect induced by the ceria nanoparticles has been evaluated on two cell lines, D407 (human retinal pigment epithelial) and B16-F10 (melanoma murine). The results make the as-obtained ceria nanoparticles promising candidates for biomedical applications. Acknowledgments: This research was supported by UEFISCDI Project No. PN-II-RU-TE-2014-4-0944, Contract No 16/01.10.2015

R.9.55
13:30
Authors : D. Istrati1, R. Cristescu*2, G. Dorcioman2, C. Popescu2, G. Socol2, M.C. Chifiriuc3, C. Bleotu4, A.M. Grumezescu5, B. Vasile5, G. Voicu5 A. Fudulu1, D.E. Mihaiescu1 and D.B. Chrisey6
Affiliations : 1Department of Organic Chemistry ?Costin Nenitescu? Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Polizu Street No. 1-7, 011061 Bucharest, Romania 2National Institute for Lasers, Plasma, and Radiation Physics (INFLPR), Atomistilor Street, No. 409, 77125, Bucharest, Romania 3Department of Microbiology?Immunology, Faculty of Biology, University of Bucharest, Romania; Research Institute of the University of Bucharest (ICUB), Bucharest, Romania 4Institute of Virology St. S. Nicolau, Bucharest, Romania 5Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Polizu Street No. 1-7, 011061 Bucharest, Romania 6Department of Physics and Engineering Physics, Tulane University, New Orleans, LA, USA

Resume : We report on the fabrication of two types of Fe3O4 / para-aminobenzoic acid core-shell nanoparticles covered with a secondary intermediate silver layer. The final organic shells were built by phthalocyanine and flavonoid type compounds, respectively. High quality thin films of the final assembled core-shell nanomaterials have been obtained by MAPLE (matrix-assisted pulsed laser evaporation) and ESI (electrospray) deposition methods, on silicon and optical glass substrates. The intermediate and final nanostructures have been characterized by XRD, FT-IR, UV-VIS, HPLC-MS, DLS, HRTEM. MAPLE- and ESI-deposited thin coatings have been characterized by FT-IR microscopy, SEM, and AFM. The core-shell magnetic nanoparticles and obtained thin films have been investigated in vitro for their microbicidal (minimal inhibitory concentration assay) and anti-biofilm (microtiter assay of the minimal biofilm eradication concentration) properties on a large panel of bacterial and fungal strains antioxidant activity, as well as for their influence on the mammalian cells morphology, viability and proliferation (cytotoxicity, cellular cycle assay). Our results revealed that the multifunctional nanostructures proved both antioxidant and antimicrobial activities and a good biocompatibility. Therefore, the obtained thin films could be further used for the development of novel bioactive materials, with antimicrobial and antioxidant properties, that could be useful for a wide range of applications, in the prevention, control or eradication of the initial adherence and further formation of microbial biofilms, frequently involved in the microbial contamination of different media and products, as well as in the etiology of chronic and hard to treat infections.

R.9.56
13:30
Authors : Ahmed Al-Kattan(1), Tarek Baati(2), Yury Ryabchikov(1), Marie-Anne Estève(2), Diane Braguer(2) and Andrei V. Kabashin(1).
Affiliations : (1)Aix Marseille Université, CNRS, LP3 UMR 7341, Campus de Luminy, 13288, Marseille Cedex 9; (2)Aix Marseille Université, INSERM, CRO2 UMR 911, Faculté de Pharmacie, 13385, Marseille Cedex 5

Resume : In this contribution we demonstrated the possibility to obtain ultra-pure inorganic particles based-on Si-NPs by femtosecond laser assisted method in aqueous solution. Their physico-chemical properties were rigorously characterized by numerous technics such as TEM-XRD, XPS, and DLS/Zeta potential method. The results showed that Si-NPs appeared as crystalized Si spherical form with narrow size distribution around 50 nm and with surface charge close to -35 mV. In addition, by monitoring the dissolved oxygen in synthesis medium we demonstrated the possibility to control their stability duration in biological matrix by modulate their thickness oxide shell (SiOx) on their surface. Concerning their biological properties, in vitro tests were performed on human microvascular endothelial cells (HMEC) in order to assess their safety/cytotoxicity properties. Only 20 % decrease in cell survival was observed after 72h of incubation up to 50 µg/mL. In addition, their fate in term of biodistribution and biodegradability was completely assessed throw a systematic in vivo study realized on nude mice. The physiological and histological analysis showed that the Si-NPs not induce oxidative stress damage. These encouraging results contribute to develop promising biocompatible and biodegradable nanosystems for potential applications in nanomedicine.

R.9.57
13:30
Authors : J.-F. Berret
Affiliations : Matière et Systèmes Complexes, UMR 7057 CNRS Université Denis Diderot Paris-VII Bâtiment Condorcet 10 rue Alice Domon et Léonie Duquet, 75205 Paris (France)

Resume : The emergence of novel materials and processing at the nanoscale has set the conditions for the fabrication of a wide range of nano-objects and multilevel nanostructured networks. Here we report a simple and versatile waterborne synthesis of highly persistent superparamagnetic magnetic wires following the concept of electrostatic ??desalting transition?? [1]. The wires have diameters of 400 nm and lengths comprised between 1 and 500 µm. When submitted to a magnetic field, the wires behave as embedded rheometers and represent interesting sensors for micro-rheology. We develop the technique of rotational magnetic spectroscopy to measure the shear viscosity of simple and complex fluids, including water-gycerol mixtures, viscoelastic surfactant solutions and polysaccharide gels. With increasing frequency, the magnetic wires exhibit a rotational instability between a synchronous and an asynchronous regime of rotation. The critical frequency between these regimes varies as ?C ~ H^2/?L^2 where H is the magnetic excitation, ? the viscosity and L the wire length, and provides an accurate measure of the static shear viscosity. Fluids of biological relevance, e.g. intracellular medium of cells or pulmonary surfactant are also studied, showing that the technique can be useful for biomechanical studies [3]. [1] J. Fresnais, J.-F. Berret, B. Frka-Petesic, O. Sandre, R. Perzynski, Adv. Mater. 20 (2008) 3877 ? 3881 [2] L. Chevry, N. K. Sampathkumar, A. Cebers and J.-F. Berret, , Phys. Rev. E 88, 062306 (2013) [3] J.-F. Berret, Nature Comm. 7, 10134 (2016)

R.9.58
13:30
Authors : Alicja E. Kownacka(a), Benjamin P. Burke(ab), Juozas Domarkas(ac), Mark Lorch(a), Martin Pickles(d), Peter Gibbs(d), Simone Mastrogiacomo(e), Frank Walboomers(e), Stephen J. Archibald*(ab)
Affiliations : (a)Department of Chemistry, University of Hull, Cottingham Road, Hull, HU6 7RX, UK; (b)Positron Emission Tomography Research Centre, University of Hull, Cottingham Road, Hull, HU6 7RX, UK; (c)Centre for Cardiovascular and Metabolic Research, Hull University, Cottingham Road, Hull, HU6 7RX, UK; (d)Centre for Magnetic Resonance Investigations, Hull Royal Infirmary, University of Hull, Hull, HU3 2JZ, UK; (e)University of Nijmegen, Department of Biomaterials, Heyendaalseweg 135, 6500 HB Nijmegen, The Netherlands.

Resume : Tissue engineered constructs for soft/hard reconstructions cannot easily be visualised by most of the available imaging modalities when implanted into a living system. Their observation in vivo is crucial because it could allow monitoring of their behaviour and integration with surrounding tissues in a non-invasive manner. Gadolinium oxide nanoparticles have gained significant attention as contrast agents because of strong T1 signal enhancement (MRI) and a high X-ray attenuation coefficient (CT) making them highly appropriate for biomedical imaging of tissue engineering constructs. Surface functionalisation by addition of bisphosphonate groups can create systems which can also have therapeutic effects, for example bone regeneration. Bisphosphonate linkers can also be modified to introduce short half-life positron or gamma emitting radioisotopes giving an additional imaging modality to detect the nanoparticles. Gadolinium oxide has been synthesised via a polyol approach forming ultra-small nanoparticles with high T1 contrast enhancement, which was measured at 11.7 T in a preclinical scanner. Colloidal stability was ensured by coating with siloxane derivatives and subsequent reaction with an alendronate derivative making the construct attractive for bone tissue targeting and thus, visualisation of target area by two imaging modalities: CT and MR. Presented nanoparticles offer advantages for longitudinal visualisation of various tissue engineering constructs in vivo.

R.9.59
13:30
Authors : Antonio Aires,(a) David Cabrera,(a) Laura C. Alonso-Pardo,(a) Aitziber L. Cortajarena (a,b) and Francisco J. Teran,(a,b)
Affiliations : (a)- iMdea Nanociencia, Campus Universitario de Cantoblanco, 28049 Madrid, Spain (b)- Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), 28049 Madrid, Spain

Resume : Nanotechnology has brought countless novel applications regarding therapeutic, diagnostic and/or sensing nanotools. In particular, nanoparticle engineering allows to synthesize nanocrystals with customized physical, chemical and/or biological functionalities, which are generally well characterized in in vitro studies. However, when nanoparticles are injected in animal models they show a disappointing loss of efficacy and/or an increase of toxicity. The causes of this fact are related to the interaction of the nanoparticle surface with proteins, enzymes and/or ions present into the blood stream, which generally turns out in the nanoparticle aggregation and consequently into nanoparticle clearance. Here, we assess the colloidal stability of 15 commercial iron oxide nanoparticles (IONP) coated with different biocompatible materials under in vivo simulated conditions. We check their physico-chemical properties when IONP are incubated in human blood plasma (HBP) and physiological aqueous dispersion (phosphate buffered saline, PBS) for 1 hour at 37ºC. We observe that the value and sign of the intrinsic IONP surface charge rule the fate of their colloidal stability in HBP and PBS. When IONP are dispersed in HBP, protein adsorption occurs for IONP independently of their sign and value of their net surface charge. The formation of the protein corona provides a given net surface charge and sign for all IONP coatings. The sign of the net surface charge does not influence the organic mass increments but it tightly governs IONP aggregation, which remarkably increases for IONP with positive surface charge. When IONP are dispersed in PBS, the hydrophilicity of the coating determines their colloidal stability required, which is a key requirement to perform their injection under in vivo suitable colloidal conditions. Our results provide the colloidal reasons why neutrally charged and hydrophilic coatings provide the best features required for IONP surface in in vivo experiments.

R.9.60
13:30
Authors : Janire Alkorta, Laura Sánchez-Abella, Adrián Peréz-San Vicente, Damien Dupin, Iraida Loinaz, Jose-Ramón Leiza
Affiliations : IK4-CIDETEC; IK4-CIDETEC; IK4-CIDETEC; IK4-CIDETEC; IK4-CIDETEC; POLYMAT

Resume : Colloidal stability in physiological fluids is often difficult to achieve, mainly due to their high salt concentration. Polymeric stabilisers are commonly used to tackle this problem, e.g. pegylation. More recently, macro-chain transfer agent (macro-CTA), which consists in a highly hydrophilic homopolymer synthesized via Reversible Addition-Fragmentation Transfer (RAFT) polymerization, have been used as steric stabilizer for the aqueous emulsion polymerization of hydrophobic co-monomers with > 90 % incorporation. This technique has been widely used to obtain self-stabilised particles (or ?hairy particles?), due to its well-defined architecture and nature, in a broad variety of ?high-tech? application areas such as optical data storage, security encryption, photonic crystals, and biotechnological or medical applications. The apparent core-shell structure of these hairy particles allows the periphery of the particles to be easily functionalised. Self-stabilized particles prepared by emulsion polymerization using poly[oligo(ethylene glycol) methacrylate] macro-CTA as polymeric stabilizer were successfully produced by varying reaction parameters such as co-monomer mixture, type of radical initiators, and amount of macro-CTA stabiliser. The resulting latex particles have been characterized in terms of particle size, Zeta potential, colloidal stability, Tg and amount of stabilisers. MTS and LIVE/DEAD assay have demonstrated the low toxicity of these self-stabilized particles.

R.9.61
13:30
Authors : Xinyu Zhao, Mei Chee Tan*
Affiliations : Engineering Product Development, Singapore University of Technology and Design, Singapore, 8 Somapah Rd, Singapore 487372

Resume : Multi-modal imaging is an emerging area that integrates multiple imaging modalities to simultaneously capture visual information over many spatial scales. Luminescence imaging is a well-established, fast visualization technique, which can be easily adapted using portable devices and used for real-time surgical guidance. Compared to ultraviolet and visible light, short wavelength infrared (SWIR) has deeper penetration depths, which facilitates resolving anatomical features located up to 1 cm beneath the skin. In contrast, penetration depths of up to 5 cm can be achieved by using an emerging optical imaging modality known as photoacoustic (PA) imaging. PA imaging that converts laser energy into acoustic waves can be detected using ultrasound and used to image tissues with a high spatial resolution and better contrast at deeper penetration depth because ultrasound scattering is two to three orders of magnitude weaker than UV and visible optical scattering in tissues. Rare-earth doped CaF2 nanophosphors with enhanced SWIR emission have a promising potential for biomedical applications in diagnostics and deep tissue imaging due to their low vibrational energy, large optical transparency and superior biocompatibility. Highly emissive SWIR-emitting CaF2 nanophosphors is critical to enhancing the luminescence detection resolution and achieving deeper penetration depth for deep tissue imaging. The PA contrast that can be achieved using these CaF2 nanophosphors depends strongly on the absorption and vibrational characteristics as well as particle size and morphology. In our presentation, we will discuss the synthesis of CaF2 nanophosphors with enhanced SWIR emission using a tri-dopant scheme incorporating Ce, Yb and Er rare earth dopants. Next, the luminescence and PA properties of these as-synthesized CaF2 nanophosphors were measured to evaluate their feasibility as dual-modal contrast agents for luminescence and PA imaging to achieve high contrast, temporal and spatial resolution and deeper detection depth.

R.9.62
13:30
Authors : Jin Hu, Weiping Gao
Affiliations : Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China

Resume : Therapeutic proteins are widely used in the field of diseases treatment due to their high specificity and bioactivity. A major disadvantage of proteins is their instability to external stressors during storage, transport and use. To overcome the problems, we report site-specific in situ growth of a polymer from a cyclized protein with improved in vitro stability and in vivo tumor retention. A linear green fluorescence protein (l-GFP) was genetically engineered, where two sortase A recognition substrates, pentaglycine and LPETG were fused to the N- and C-termini of GFP for sortase-catalyzed cyclization, a free cysteine residue was introduced near the C-terminus for site-specific installation of the atom transfer radical polymerization (ATRP) initiator. The maleimide-functionalized initiator was selectively attached to the cysteine residue to form a macroinitiator (c-GFP-Br), followed by in situ ATRP of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) to generate a site-specific (C-terminal) and stoichiometric (1:1) c-GFP-POEGMA conjugate with almost quantitative conversion. Notably, the c-GFP-POEGMA conjugate displayed 9- and 310-fold increases in thermal stability compared with l-GFP and l-GFP-POEGMA, respectively, indicating that c-GFP-POEGMA was much more resistant to thermal denaturation than l-GFP and l-GFP-POEGMA. Besides, in a tumor-bearing mice model, the c-GFP-POEGMA conjugate showed significantly improved tumor retention than the l-GFP and l-GFP-POEGMA. The fluorescence of l-GFP in tumors rapidly decreased to nearly zero within 3 h, whereas the fluorescence of c-GFP-POEGMA and l-GFP-POEGMA in tumors slightly decreased and was detectable even after 48 h post administration. The fluorescence of c-GFP-POEGMA in tumors was over 6-fold higher than that of l-GFP-POEGMA at 60 h post injection, which might be attributed to the improved tumor retention of c-GFP over l-GFP. The data indicated that c-GFP-POEGMA had much better tumor retention than l-GFP and l-GFP-POEGMA. In conclusion, we develop a unique and general route to synthesize a site-specific and stoichiometric cyclic protein polymer conjugate with improved in vitro and in vivo stability via sortase-catalyzed cyclization followed by site-specific in situ ATRP.

R.9.63
13:30
Authors : Cornelia Nichita1,2, Adriana Balan1 , Ana Cucu1, Catalin Ceaus1 Serban Stamatin1,3 and Ioan Stamatin1
Affiliations : 1University of Bucharest,Faculty of Physics, 3Nano-SAE Research Centre PO Box MG-38, Bucharest-Magurele, Romania 2 National Institute for Chemical-Pharmaceutical Research and Development, 112VitanStreet, 031299, Bucharest, Romania, e-mail: cornelianichita@yahoo.com 3 Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, College Green, Dublin 2, Ireland

Resume : Graphene and its derivatives (graphene oxides, nanoplatelets) have attracted research interest for their potential applications in nanomedicine, biotechnologies, pharmacology. Earlier studies focused on toxicity and biocompatibility. However, little information of their antioxidant activity and relation with different molecules well recognized as free radical scavengers such as OH. Herein are performed a comprehensive study on the antioxidant activity, measured by chemiluminescence, for a couple of hosts (graphene, graphene oxide) and guests (flavone-quercetin, rutin; flavanone-hesperidin, naringenin) selfassembled in high density ultrasonic field. The results have shown a high specific activity for graphene oxide and no effect for graphene. Thai is a consequence of the functional groups COOH and OH induced by solvo-thermal exfoliation during oxidation process of the carbon raw materials. In addition is proved that free radical scavenging is as mediated by proton transfer to the couple host-guest and not via electron transfer.

R.9.64
13:30
Authors : Beata Kalska-Szostko1, Urszula Klekotka1, Dariusz Satua2
Affiliations : University of Bialystok, Institute of Chemistry, Ciolkowskiego 1K, 15-245 Bialystok, Poland1* University of Bialystok, Department of Physics, Ciolkowskiego 1L 15-245 Bialystok, Poland2

Resume : Preparation of well-defined nanoparticles is a big challenge for many scientists. Especially in case when structure is divided into the core and shell. However, this case is most interesting because of possibility to combine many properties in one low dimensional structure. Presented in this paper particles of core-shell structure have many interesting properties, among other we can stress: specific optical, magnetic, electrical, and mechanical one. In addition, few of them can be combined in one spices [1]. Discussed core-shell ferrite nanoparticles, has various composition of the core -mixture of Fe3+, Fe2+ and Men+ ions (where Me = Co2+, Co3+, Mn2+, Mn3+ or Ni2+). Elements were mixed in such way, that crystalline structure of magnetite is preserved. Shell layer was composed of magnetite. Applied synthesis was based on step-by-step seeds method with use of proper metal acetylacetonate salts in organic solution [2]. Characterization of the nanoparticles was done by Transmission Electron Microscopy, X-ray diffraction, Infrared spectroscopy, and Mössbauer spectroscopy.

R.9.65
13:30
Authors : Peep Uudeküll (1), Helina Seemen (1), Hugo Mändar (1), Joosep Link (3), Mariliis Klaas (2), Rait Vetik (2), Viljar Jaks (2), Raivo Stern (3), Tanel Tätte (1), Aile Tamm (1)
Affiliations : (1) Institute of Physics, University of Tartu, Ravila 14c, 50411, Tartu, Estonia (2) Institute of Molecular and Cell Biology, University of Tartu, Riia 23B, 51010, Tartu, Estonia (3) National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia

Resume : During the past decades the use of magnetic fine particles in biomedical applications has gone through rapid growth. However, uniform size micro- and mesoscale particles have attracted far less attention than nanoparticles. For instance, transition metal mesoparticles are used in applications such as magnetic cell separation, drug targeting, magnetic fluid hyperthermia, etc. [1]. We report the synthesis of nickel mesoparticles (primary size 100-400 nm) by nonaqueous liquid phase chemical method (the benzyl alcohol method) [2]. Being developed for magnetically guided biomedical applications, the Ni particles were coated by conformal and antimicrobial thin TiO2 film grown by atomic layer deposition. Spherical Ni particles essentially retained their size and crystal structure after the deposition of TiO2 film at elevated temperatures. The sensitivity of TiO2-coated Ni particles in terms of their response to external magnetic fields was slightly increased compared to the uncoated powder. We plan to carry out safety tests as a next step of our studies. Primary human skin fibroblasts will be co-cultured with ALD-coated and uncoated particles and the number of viable cells in each sample will be quantified by a luminescent cell viability assay. [1] B. Kozissnik and J. Dobson; MRS Bull., vol. 38, no. 11, pp. 927–932, 2013. [2] N. Pinna, et. al.; J. Sol-Gel Sci. Technol., vol. 57, no. 3, pp. 323–329, 2011.

R.9.66
13:30
Authors : A. Essyed1, M. A. Ait Kerroum1, K. Lasri2, K. Elmaalam2, M. Benali2, O. Mounkachi2, M. Hamdoun2, A. Benyoussef1,2 and M. Benaissa1
Affiliations : 1: L.M.P.H.E, Department of physics, Faculty of Sciences, University Mohammed V, Rabat, Morocco ; 2: Institute of Nanomaterials and Nanotechnology, MASCIR, Rabat, Morocco

Resume : In the present study, we have synthesized nanoparticles of iron ferrite by the sol-gel method with Polyethylene glycol (PEG-4000) as solvent and ferric iron nitrate Fe(NO3)3 as presursor with different concentrations. Above a temperature of 100°C, Fe3O4 was obtained directly without calcination. XRD pattern shows the presence of an intense peak corresponding to the known (311) crystallographic orientation of the Fe3O4 magnetite spinel phase. When followed by heat treatment at 400°C under atmospheric pressure, a phase transfomation to α- Fe2O3 was noticed due to the presence of the (104) crystallographic orientation in the XRD pattern. A mean size of about 12 nm of the magnetite nanoparticles was directly measured by TEM experiments, which is consistent with the value estimated from XRD analysis. Magnetic properties of the synthesized magnetite nanoparticles, measured using a SQUID magnetometer, showed a superpamagnetic behavior. All these features make the synthesized nanoparticles good candidates in nanomedicine.

R.9.67
13:30
Authors : A.M. Holban3,4, V. Grumezescu1,2, C. Saviuc3,4, L.M. Ditu3,4, C. Curutiu3,4, A.M. Grumezescu2, M.C. Chifiriuc3,4, V. Lazar3,4
Affiliations : 1Lasers Department, National Institute for Lasers, Plasma & Radiation Physics, P.O. Box MG-36, Magurele, Bucharest, Romania 2Department of Science and Engineering of Oxidic Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1–7 Polizu Street, 011061 Bucharest, Romania 3Microbiology Immunology Department, Faculty of Biology, University of Bucharest, 1–3 Portocalelor Lane, Sector 5, 77206 Bucharest, Romania 4Research Institute of the University of Bucharest, Spl. Independentei 91-95, Bucharest, Romania

Resume : Aim: to develop, characterize and evaluate an iron oxide nanosystem for the efficient stabilization and delivery of natural volatile compounds with antimicrobial effect. Materials and methods: Iron oxide nanoparticles were prepared by an adapted co-precipitation method and functionalized with limonene. The obtained nanosystem was characterized by High Resolution Transmission Electron Microscopy (HR-TEM), Scanning Electron Microscopy (SEM), Thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The antimicrobial effect was tested for both free-floating (agar diffusion test and flow cytometry) and sessile bacterial cells belonging to Pseudomonas aeruginosa clinical and reference strains (Cravioto, microtiter and viable counts assay methods). Results: the obtained nanobiosystem inhibited the development of both free-floating and attached microbial cells in a strain and dose-dependent manner, as revealed by: i) the decrease of the minimum inhibitory concentration of the active compound by up to two folds, the most significant effect being observed for the antibiotic susceptible P. aeruginosa strains; ii) the reduced biofilm formation of all tested strains, but however a much higher amount of bioactive nanosystem being necessary to inhibit biofilm formation in case of antibiotic resistant strains; iii) modulation of the efflux pumps in a dose and strain dependent manner, limonene functionalized nanoparticles exhibiting a synergic effect with antibiotics.

R.9.68
13:30
Authors : E. S. Bronze-Uhle,1,2 B. C. Costa,1 V. F. Ximenes1 and P. L. Lisboa-Filho 1,2 *
Affiliations : 1 UNESP - Univ Estadual Paulista, POSMAT - Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, Bauru, SP, Brazil 2 DF-FC, UNESP - Univ Estadual Paulista, Av. Eng. Luiz Edmundo Carrijo Coube 14-01, 17033-360 Bauru, SP, Brazil.

Resume : Transportation systems based on albumin nanoparticles represent an important strategy since significant amounts of drug can be incorporated within the particle, as a function of different albumin binding sites. Bovine Serum Albumin (BSA) is highly water soluble and binds noncovalently with drugs or an inorganic material for the efficient drug delivery in various areas the affected body. Historically, albumin has been extensively applied as biodegradable anti-cancer drug charger because of its excellent biocompatibility and high stability in blood can accumulate in malignant or inflamed tissue. [1] [2] [3] Due to the well defined structure of the protein, containing charged amino acids, the albumin nanoparticles may allow electrostatic adsorption molecules negatively or positively charged without the application of other compounds on the surface. Therefore significant amounts of drug can be incorporated within the particle, as a function of different albumin binding sites. In this work we study the synthesis of bovine serum albumin nanoparticles, by desolvation process, containing salicylic acid as the active agent. Salicylic acid (SA) and salicylates are components of various plants and have been used for medication with anti-inflammatory, antibacterial and antifungal properties. Commercially, salicylic acid salicylates are an active metabolite of aspirin (acetyl salicylic acid) and have been used since century V. However, when administered orally to adults (usual dose provided by the manufacturer), decomposes 50% salicylates. [4] Then, over time there is a search to develop new systems in order to improve the bioavailability of SA and salicylates in the human body. To this end, in synthetic procedure, the pH ranged synthesis (5.4, 7.4 and 9.0) in order to evaluate the influence on the size and stability of the formed nanoparticles. The samples were analyzed using by FE-SEM, TEM, FTIR, Zeta Potential and DLS. Through fluorescence was possible to analyze the release of salicylic acid "in vitro" in PBS solution. The chemical morphology characterization results and the “in vitro” release studies indicate the potential use of these nanoparticles, as drug carriers in biological systems requiring a fast release of salicylic acid. Keywords: albumin nanoparticles, salicylic acid entrapped, drug delivery; [1] R. Xu, M. Fisher, R.L. Juliano, Bioconjug. Chem. 22 (2011) 870. [2] G.V. Patil, Drug Dev. Res. 58 (2003) 219. [3] J.M. Irache, M. Merodio, A. Arnedo, M.A. Camapanero, M. Mirshahi, S. Espuelas, Mini Rev. Med. Chem. 5 (2005) 293. [4] M. A. Rogers, Y. F. Yan, K. Ben-Elazar, Y. Lan, J. Faig, K. Smith, K. E. Uhrich, Biomacromolecules, 2014, 15, 3406−3411. eriuhle@fc.unesp.br – Av. Eng. Luiz Edmundo Carrijo Coube, 14-01, 17033-360 Bauru – SP – Brazil Tel: +55-14-3103-6084, ramal. 34; Fax: +55-14-31036094.

R.9.69
13:30
Authors : Fadwa El Haddassi1, Eoin Fox1, Jose Hierrezuelo1, Jacek Stolarczyk2, Andras Deak3, and Dermot Brougham4*
Affiliations : 1 School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland. 2 Photonics and Optoelectronics Group, Department of Physics and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität Munich, Amalienstrasse 54, 80799 Munich, Germany 3 Institute for Technical Physics and Materials Science, HAS Centre for Energy Research, P.O. Box 49, H-1525 Budapest, Hungary 4 School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.

Resume : Clusters or assemblies of nanoparticles exhibit unique features which arise from the enhancement of properties of single nanoparticles or due to emergent collective properties, which may open up new applications. Hence robust, cheap and scaleable colloidal assembly methods to produce monodisperse multi-component nanoparticle assemblies are required. In this talk we will review the role of NP interactions in controlling cluster formation, classify the assembly mechanisms, [1] and describe recent advances in one approach to assembly, competitive stabilizer desorption (CSD). [2-4] In CSD the relative monodispersity of the assemblies improves, as compared to the starting particles, and assemblies can be prepared over a broad size range. CSD uses cheap materials, is reproducible, robust and scaleable, and is applicable to a range of NP types and combinations. The performance of suspension of nanoparticle assemblies, prepared using CSD, for MRI and hyperthermic applications will be discussed. 1. J. K. Stolarczyk, A. Deak, D. F. Brougham. Adv. Mater., 2016, DOI:10.1002/adma.201505350 2. C. J. Meledandri, J. K. Stolarczyk, D. F. Brougham, ACS Nano 2011, 5, 1747-1755. 3. J. K. Stolarczyk, S. K. Ghosh, D. F. Brougham, Angew. Chem. Int. Ed. 2009, 48, 175-178. 4. T. Ninjbadgar, E. K. Fox, J. Hierrezuelo, F. El Haddassi, D. F. Brougham. J. Mater. Chem. B, 2015, 3, 8638 - 8643.

R.9.70
13:30
Authors : G. Muscas1,2, N. Yaacoub4, F. Sayed4, R. Sayed Hassan4, J.M. Greneche4, C. Cannas3, A. Musinu3, S. Casciardi5, C. Sangregorio6 and D. Peddis1,7
Affiliations : 1 Istituto di Struttura della Materia - CNR, 00016 Monterotondo Scalo (RM), Italy 2 Department of Engineering Sciences, Uppsala University, Box 534, SE-751 21, Uppsala, Sweden 3Dip. di Sci. Chim. e Geo. and INSTM, Univ. di Cagliari, S.P. Monserrato-Sestu km , 09042 Monserrato, Itayl 4LUNAM, Université du Maine, IMMM CNRS UMR-6283, F-72085, Le Mans, France 5DOEM, Epidemiology and Hygiene, INAIL Research), Monte Porzio Catone, Rome, Italy 6Istituto di Chimica dei Composti Organo-Metallici, Consiglio Nazionale delle Ricerche, via Madonna del Piano 10, I-50019 Sesto Fiorentino, Italy 7 Vinca Institute, University of Belgrade, POB 522, 11001 Belgrade, Serbia

Resume : Magnetic properties of iron oxide nanoparticles with spinel structure are strictly related to a complex interplay between cationic distribution and the presence of a non-collinear spin structure (spin canting). With the aim to gain better insight into the effect of the magnetic structure on magnetic properties, in this paper we investigated a family of small crystalline ferrite nanoparticles of the formula CoxNi1−xFe2O4 (0 ≤ x ≤ 1) having equal size (≈4.5 nm) and spherical-like shape. The field dependence of magnetization at low temperatures indicated a clear increase of magnetocrystalline anisotropy and saturation magnetiza- tion (higher than the bulk value for CoFe2O4: ∼130 A m2 kg−1) with the increase of cobalt content. The magnetic structure of nanoparticles has been investigated by Mössbauer spectroscopy under an intense magnetic field (8 T) at a low temperature (10 K). The magnetic properties have been explained in terms of an evolution of the magnetic structure with the increase of cobalt content. In addition a direct correlation between cationic distribution and spin canting has been proposed, explaining the presence of a non- collinear spin structure in terms of superexchange interaction energy produced by the average cationic distribution and vacancies in the spinel structure.

R.9.71
13:30
Authors : A. Guerrini(1), C. Innocenti(1), E. Fantechi(1), B. Tenci(2), T. Mello(2), L. di Cesare Mannelli(2), E. Falvo(3), P. Ceci(3), C. Sangregorio(4)
Affiliations : (1) INSTM and Dip. di Chimica ?U. Schiff?, Univ. di Firenze, 50019, Italy (2) Dip. NEUROFARBA - Sez. Farmacologia e Tossicologia, Univ. di Firenze, 50100, Italy (3) CNR-IBPM, Dip. di Scienze Biochimiche ?A. Rossi Fanelli?, Univ. di Roma ?Sapienza?, 00185, Italy (4) CNR-ICCOM and INSTM, Sesto Fiorentino (FI), 50019 Italy

Resume : Iron oxide nanoparticles, NP, mineralized within human H-chain ferritin, HFt, represent a viable platform to develop novel theranostic agents, as they offer multiple advantages in terms of stability, biocompatibility and easiness of functionalization. However, a major limitation is that the NP size cannot exceed the inner diameter (ca. 8 nm), a too low size to produce a sizable amount of heat. In order to overcome this drawback while still exploiting the advantages provided by HFt, we developed two different approaches: first, we increased the magnetic anisotropy of the NPs by doping with Co2+ ions (CoNP-HFt); second, we conjugated HFt on larger (15 nm), chemically synthesized, maghemite NPs (HFt-NP). In vitro tests showed that both constructs were highly biocompatible. The hyperthermic properties of CoNP-HFt and HFt-NPs were investigated through calorimetric technique and related to structural and magnetic properties. A doping of 5% was found to enhance the hyperthermic efficiency of CoNP-HFt and to induce a significant reduction of cell viability when exposed to an alternating field. On the other hand, despite of the much larger hyperthermic efficiency, HFt-NP were found to affect cell viability only when internalized in large amount, as confirmed by confocal microscopy. These results enlighten the fundamental role of cell-NP interactions with respect to large hyperthermic efficiency. Research funded by RINAME (MIUR), BaTMAN (CARIPLO n.2013-0752) and CNR-CNPq projects.

R.9.72
13:30
Authors : James A. Tyson; Vincenzo Mirabello; David G. Calatayud; Gabriele Kociok-Köhn; Haobo, Ge; Stanley W. Botchway; G. Dan Panto?; Sofia I. Pascu.
Affiliations : James A. Tyson; Vincenzo Mirabello; David G. Calatayud; Gabriele Kociok-Köhn; Haobo, Ge; G. Dan Panto?; Sofia I. Pascu. a. Department of Chemistry, University of Bath, Claverton Down, BA2 7AY, UK Stanley W. Botchway b. Central Laser Facility, Rutherford Appleton Laboratory, Research Complex at Harwell, STFC Didcot OX11 0QX, UK

Resume : We report the assemblies of novel nanohybrid materials formed between planar carbon systems (PCS) such as coronene or TRGO and a series of new halogenated ?- amino acid tagged NDI chromophores. The functionalization of graphene-like systems with NDI chromophores can be facilitated via a mechanism of Föster resonance energy transfer (FRET) whereby photoinduced electron transfer takes place. UV-Vis, Fluorescence spectroscopies and fluorescence lifetime decay measurements rationalised such FRET mechanisms and elucidated the role of coronene and TRGO as a quenching materials. The morphology of organic nanoparticles generated from the complexation of NDIs with coronene and TRGO nanosheets were also studied by SEM and TEM. NMR experiments allowed for studies into the kinetics of the supramolecular association between chromophores and PCS. Confocal fluorescence microscopy studies carried out on NDI-coronene and NDI-TRGO show that our nanocomposites are up-taken in PC-3 cells suggesting their potential as prostate cancer bioimaging agents. MTT assays suggest that the deliberate functionalization of the surface of TRGO and coronene with phenylalanine NDIs significantly improves the biocompatibility of such graphene-like nanocomposites with respect to the pristine TRGO and coronene. The results here presented may lead to a new prospective in the use of the functionalization processes to achieve fluorogenic composite materials based on planer carbon materials for biological application The authors would like to thanks ERC Consolidator grant scheme (O2Sense to Sofia Pascu).

R.9.73
13:30
Authors : Maria Russo 1,2 Paolo Antonio Netti 1,2,3 Enza Torino 2,3
Affiliations : 1 Department of Chemical Engineering, Materials and Industrial Production, University of Naples Federico II, Naples 80125, Italy 2 Istituto Italiano di Tecnologia, Center for Advanced Biomaterials for Healthcare IIT@CRIB, Naples 80125, Italy 3 Interdisciplinary Research Center on Biomaterials, University of Naples Federico II, Naples 80125, Italy

Resume : The ability to tune the properties of hydrogel nanostructures confining Gd-DTPA and to impact on the relaxometric properties of these category of active compounds can introduce a new class of MRI Contrast Agents (CAs). Although only few efforts have been made to refine the characteristics of hydrogels nanostructures containing CAs, their exceptional hydrophilic properties could strongly improve the relaxometric properties of CAs by influencing the relaxation time of water protons. Here, we propose a general and adjustable strategy to obtain intravascularly-injectable and biocompatible crosslinked hydrogel nanoparticles confining Gd-DTPA. Through a microfluidic flow focusing approach a fine-tuning of all species is adjusted to control very precisely the competition between the nanoprecipitation behavior and the crosslinking reaction. In this fashionable way, we achieve the optimization of the confinement of Gadolinum CAs within the polymer matrix and, at the same time, the modulation of the release behavior and the stability of hydrogel nanoparticles. A mean particle size smaller than 40 nm and improved MRI characteristics are obtained without the chemical modification of the chelates, achieving a signal intensity in r1 12 times larger than that of the commercial MRI contrast agent (Magnevist) at the common field of clinical MRI. In addition, the obtained hydrogel nanostructures confining Gd-DTPA provide tissue specificity and reduced nephrotoxicity.

R.9.74
13:30
Authors : NGUYEN TK THANH
Affiliations : Biophysics Group, Department of Physics and Astronomy and UCL Healthcare Biomagnetic and Nanomaterials Laboratory http://www.ntk-thanh.co.uk, Email: ntk.thanh@ucl.ac.uk

Resume : In this presentation I will the most recent results of our group on synthesis and functionalisation of nanoparticles for biomedical applications. Ref: 1. R. Hachani, M. Lowdell, M. Birchall, A. Hervault, D. Merts, S. Begin-Colin, N.T.K. Thanh*. (2016) Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles for potential MRI contrast agents. Nanoscale. DOI: 10.1039/c5nr03867g. Open Access 2. R. M. Pallares, X. Su, S. H. Lim, N. T. K Thanh* (2016) Fine-Tuning Gold Nanorods Dimensions and Plasmonic Properties Using the Hofmeister Salt Effects. Journal of Material Chemistry C. 4: 53-61. Open access. Front Cover 3. C. Blanco-Andujar, P. Southern, D. Ortega, S.A. Nesbitt, Q.A., Pankhurst and Thanh, N. T. K*. (2016) Real -time tracking of delayed-onset cellular apoptosis induce d by intracellular magnetic hyperthermia. Nanomedicine. 11: 121-136. Open Access. 4. R. M. Pallares, S. L. Kong, H. R. Tan, Thanh, N.T.K, Y. Lu and X. Su (2015) A plasmonic nanosensor with inverse sensitivity for circulating cell-free DNA quantification. Chemical Communications. 51, 14524 - 14527 5. L. T. Lu, N. T. Dung, L. D. Tung, C. T. Thanh, O. K Quy, N. V. Chuc and N. T. K. Thanh* (2015) Synthesis of magnetic cobalt ferrite nanoparticles with controlled morphology, monodispersity and composition: the influence of solvent, surfactant, reductant and synthetic condition. Nanoscale. 7: 19596-19610. Open Access. Front Cover 6. R. Baber, L. Mazzei, N. T. K. Thanh, A. Gavriilidis (2015) Synthesis of silver nanoparticles in microfluidic coaxial flow reactors. RSC Advances. 5: 95585-95591. Open Acess

R.9.75
13:30
Authors : Enaam Jamal Al Dine1, 3*, Alexandra Schejn2, Thibault Roques-Carmes2, Houssam Obeid3, Tayssir Hamieh3, Joumana Toufaily3, Eric Gaffet1, Sophie Marchal4, Raphaël Schneider2, Halima Alem1
Affiliations : 1. Institut Jean Lamour (IJL), UMR CNRS 7198, Université de Lorraine, Département N2EV, Parc de Saurupt CS50840 54011 Nancy, France. 2. Laboratoire Réaction et Génie des Procédés (LRGP), UMR CNRS 7274, Université de Lorraine, 1 rue Grandville 54001 Nancy, France. 3. Laboratory of Materials, Catalysis, Environment and Analytical Methods, Faculty of Sciences I, Lebanese University, Campus Rafic Hariri, Beirut, Lebanon 4. Institut Cancérologie de Lorraine, 6 Avenue de Bourgogne CS 30519 54519 Vandœuvre-lès-Nancy, France * enaam.jamal-al-dine@univ-lorraine.fr

Resume : Multifunctional thermoresponsive nanoparticles were easily designed via activators regenerated by electron transfer atom transfer radical polymerization (ARGET- ATRP) of commercially available methacrylate derivatives from the surface of zinc oxide quantum dots (ZnO QDs). Conserving the luminescent properties of ZnO QDs, these nanoparticles showed different responsive behavior in water as well as in different media by varying the composition of the copolymer. The results also showed that below a specific concentration these nanoparticles have a very low toxicity towards healthy cells. Therefore, they could be very interesting candidates for applications in nanomedicine.

R.9.76
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Nano-based sensors : Nguyen TK Thanh - K. Chester
08:30
Authors : R. Steven Conlan
Affiliations : Swansea University Medical School

Resume : Gynaecological cancers include ovarian cancer and endometrial cancer. We have developed biological and synthetic nanomedicines to target these two diseases. To effectively diagnose and monitor cancer effective nano-based sensors are required. We have developed a graphene based sensor that offers levels of sensitivity enabling detection of circulating cancer markers including epigenetic factors. The development and integration of nanomedicines and nanodiagnostics will be discussed, including their fit with the emerging global personalised medicine agenda.

R.10.1
09:00
Authors : Tapas Sen
Affiliations : Nano-biomaterials Research Group, www.senlabs.org School of Physical Sciences and Computing University of Central Lancashire, Preston, PR1 2HE, United Kingdom

Resume : The fabrication of nanoporous / nanoparticulate composites and their applications via surface patterning with chemicals and bio-chemicals has a direct impact in bio-sensing and bio-separation. Surface patterning on nanoparticles in suspension can be a complex process due to the aggregation of the particles and their Brownian motion in the suspension. An overview of group?s research on nanomaterials and their applications in the separation of nucleic acids (DNA and RNA) from the biological cells will be presented in connection with an industrial collaboration with Q-Bioanalytic, Germany. The possibility of affinity interaction of biomolecules i.e. nucleic acid, protein, antibody, microorganisms etc. through hybrid capture will also be discussed in the context of food quality and hygiene in Bio-sensing which has recently been published in Nature publishing group (http://www.nature.com/srep/2012/120807/srep00564/full/srep00564.html?WT.ec_id=SREP-639-20120903). Separation of toxic and microbial contaminants from water and soil using nanotechnology tool will be discussed in the context of on-going multinational projects (http://senlabs.org/international-projects/ & http://nanowateratuclan.org/) in collaboration with top academic and industrial researchers from Europe, India and China. Recent development (UK Patent: 2013: GB1315407.5. & PCT/GB2014/052,630) on sensing antimicrobial nanocomposites will be discussed in connection with water technology.

R.10.2
09:20
Authors : Lin Yue Lanry Yung
Affiliations : Department of Chemical & Biomolecular Engineering, National University of Singapore

Resume : We have developed a unique DNA-assembled gold nanoparticles (AuNPs) dimer for biosensing via the dynamic light scattering (DLS) platform. Using estrogen receptor (ER), which binds specifically to a double-stranded (ds) DNA sequence containing estrogen response element (ERE), as an example, we successfully incorporated ERE sequence into the DNA linkers to bridge the AuNPs dimer for ER binding. Coupled with DLS, this AuNP dimer-based DLS detection system gave distinct readout of a single ?complex peak? in the presence of the target molecule (i.e., ER). This unique signature marked the first time that such nanostructures can be used to study transcription factor-DNA interactions, which DLS alone cannot do. This was unlike previously reported AuNP-DLS assays that gave random and broad distribution of particles size upon target binding. In addition, the ERE-containing AuNP dimers could also suppress the light-scattering signal from the unbound proteins and other interfering factors (e.g., buffer background), and has potential for sensitive detection of target proteins in complex biological samples such as cell lysates. In short, the as-developed AuNP dimer probe coupled with DLS is a simple (mix and test), rapid (readout in ~5min) and sensitive (low nM levels of ER) platform to detect sequence-specific protein-DNA binding event.

R.10.3
09:40
Authors : Fengyan Zhang
Affiliations : College of Energy, Xiamen University, Xiamen, China

Resume : To explore the most dynamic cross field of nanotechnology and life science, and to find a more practical method of fabricating nanodevices on a very large scale with advantages of low manufacturing cost, high reliability and reproducibility, we successfully fabricated a submicron IrO2 nanowire array biosensor platform by conventional complementary metal-oxide-semiconductor (CMOS) process. Single crystal IrO2 nanowire array was grown uniformly on a 6-in. wafer surface by chemical vapor deposition (CVD) method and patterned into submicron array clusters. The obtained clusters were positioned in a designed pattern similar to a multiple electrode array (MEA) format, and each was individually addressed. The fabrication method was found to be reliable, low cost and robust. The final chip showed excellent transparency, functionality and durability. These chips have been used for neuron cell stimulation and protein sensing, the experiment results will be presented.

R.10.4
09:55 Coffee break    
 
Design of theransotic nanoparticles (3) : Nguyen TK Thanh - S. Conlan
10:15
Authors : Professor Kerry Chester
Affiliations : UCL Cancer Institute, Paul O’Gorman Building University College London, 72 Huntley Street, London WC1E 6BT, U.K. http://www.ucl.ac.uk/cancer

Resume : SPIONs have exciting potential as cancer theranostic agents. SPION can be used for imaging and also induced to heat by application of an alternating magnetic field. Heat is toxic to the targeted cells, resulting in effective localized hyperthermic therapy. The feasibility and translational challenges of exploiting this nanomedicine approach to cancer treatment will be discussed.

R.11.1
10:45
Authors : Fulvio Ratto
Affiliations : Inst. Applied Physics N Carrara, Nat'l Research Council Italy

Resume : The clinical exploitation of plasmonic particles such as gold nanorods, nanoshells and nanocages has become a remarkable mission for a broad community of scientists. These particles are proposed as contrast agents for various applications in biomedical optics, including the photothermal ablation and the photoacoustic imaging of cancer, which are emerging as hopeful alternatives in oncology. At present, one of the most relevant challenges in nanomedicine is to really optimize the delivery of functional nanoparticles into tumors upon systemic administration, as a ?magic bullet?. In this context, PEGylated gold nanorods offer favorable conditions. Their hydrodynamic sizes are ideal to exploit the enhanced permeability and retention of most tumors. Besides, PEG strands enable their bio-conjugation with targeting units, such as antibodies. PEGylated and bio-conjugated gold nanorods display high specificity and blood compatibility in vitro. Therefore, their direct injection into the bloodstream has become a mainstream solution. However, after more than one decade of preclinical trials in dozens of labs, this route still remains problematic. Upon intravenous injection, more than 90% of the gold nanorods typically get captured by the mononuclear phagocyte system. More recently, the notion to exploit the natural tropism of cells such as tumor-associated macrophages, T cells, mesenchymal stem cells and neural stem cells has begun to emerge as a radical alternative. Tumor-tropic cells hold an innate ability to infiltrate tumors across all barriers with the aim to modulate their microenvironment and may be exploited as biological vehicles to take up and to deliver functional cargos. Several authors have suggested that this approach may improve the distribution of different particles both between the tumor and other parts of the body and locally within the tumor. In addition, the use of cellular vehicles implies a significant simplification of the biological interface of the plasmonic particles. Here, we disclose our recent achievements in the preparation of polycationic gold nanorods for a robust design of cellular vehicles that combine high optical absorbance, viability and chemotaxis. We discuss perspectives and possible limitations for their use as contrast agents for photoacoustic imaging, CT and photothermal treatments. We are confident that our work may inspire new solutions at the crossroads of nanomedicine and biomedical optics.

R.11.2
11:05
Authors : XU Chenjie
Affiliations : 1. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 2. NTU-NU Institute of Nanomedicine, Nanyang Technological University, Singapore

Resume : Nanoparticles are increasingly popular choices for labeling and tracking cells in biomedical applications such as cell therapy. However, all current types of nanoparticles fail to provide a real-time and noninvasive monitoring of cell status and functions while often generating false positive signals. Herein, a nanosensor platform to track the real-time expression of specific biomarkers that correlate with cell status and functions is reported. Nanosensors are synthesized by encapsulating selected sensor molecules within biodegradable polymeric nanoparticles. Upon intracellular entry, nanosensors reside within the cell cytoplasm, serving as a depot to continuously release sensor molecules for approximately 30 days. In the absence of the target biomarkers, the released sensor molecules remain ?Off?. When the biomarker(s) is expressed, a detectable signal is generated (On). As a proof-of-concepts, three nanosensor formulations based on this concept are synthesized to monitor cell viability, secretion of nitric oxide, and stem cell differentiation.

R.11.3
11:25
Authors : Richard D. Tilley
Affiliations : School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales, Sydney, NSW 2052, Australia

Resume : Bimetallic nanostructures show exciting potential as materials for effective photothermal hyperthermia therapy. This talk will discuss the seed-mediated synthesis of palladium-gold (Pd-Au) nanostructures containing multiple gold nanocrystals on highly-branched palladium seeds.[1] The nanostructures were synthesized via the addition of gold precursor to a palladium seed solution, in the presence of oleylamine which acts as both a reducing and stabilizing agent. The interaction and the electronic coupling between gold nanocrystals and between palladium and gold broadened and red-shifted the localized surface plasmon resonance (LSPR) absorption maximum of the gold nanocrystals into the near-infrared (NIR) region, to give enhanced suitability for photothermal hyperthermia therapy. Results discussed will show Pd-Au heterostructures irradiated with 808 nm laser light caused destruction of HeLa cancer cells in vitro, as well as complete destruction of tumor xenographs in mouse models in vivo for effective photothermal hyperthermia. [1] A. J. McGrath, Y-H. Chien, S. Cheong, D. A. J. Herman, J. Watt, A. M. Henning, L. O. Gloag, C-S. Yeh, R. D. Tilley, ‘Gold over Branched Palladium Nanostructures for Photothermal Cancer Therapy’ ACS Nano, 9,12283–1229, (2015).

R.11.4
11:40
Authors : Charlotte Mellier (a), Christelle Despas (b), Franck Fayon (c), Jean-Claude Scimeca (d), Olivier Gauthier (e), Jean-Michel Bouler (f), Bruno Bujoli (f)
Affiliations : (a) Graftys SA, Eiffel Park, Bâtiment D, 415 Rue Claude Nicolas Ledoux, Pôle d’activités d’Aix en Provence, 13854 Aix en Provence CEDEX 3, (France) ; (b) Nancy-Université, CNRS, UMR 7564, LCPME, 405 rue de Vandoeuvre, 54600 Villers-lès- Nancy, (France) ; (c) CNRS, UPR 3079, CEMHTI, 1D Avenue de la Recherche Scientifique, 45071 Orléans Cedex 02, (France) ; (d) Université Nice Sophia Antipolis, UMR7277 CNRS - UMR1091 INSERM, Institut de Biologie Valrose, 28 av. de Valombrose, 06107 NICE Cedex 2 (France); (e) Université de Nantes, INSERM, UMR 791, LIOAD, Faculté de Chirurgie Dentaire, BP 84215, 44042 Nantes Cedex 1, (France) ; (f) Université de Nantes, CNRS, UMR 6230, CEISAM, UFR Sciences et Techniques, 2, rue de la Houssinière, BP 92208, 44322 NANTES Cedex 3 (France)

Resume : In order to overcome the current limitations of systemic drug administrations in some clinical indications, Targeted Delivery Systems (TDS) emerge as a promising facet of the biomedical and pharmaceutical research and industry, since TDS allow controlling the location of the bioactive systems and producing efficient pharmacological effects only to specifically intended target sites, with significant therapeutic benefits and reduced side effects. In particular, the local drug release mediated by injectable TDS directly implanted on the target site, using interventional radiology procedures, is a simpler and short-term strategy, from a technical and regulatory point of view. Interestingly, it also anticipates the foreseeable increase in the use of interventional imaging machines in operating rooms. In this context, we will describe a new class of TDS for bone therapies, based on injectable calcium phosphate cements (CPCs) combined to drugs, with unique multitasking capabilities. In addition to its role as carrier to allow the controlled local elution of the drug, CPCs also act as a “calcium and phosphate ions reservoir” that promote bone repair in the bone site where it is injected. The expected feature is a high benefit/risk ratio, since only one minimally invasive injection should be necessary. Some examples will be given for the following indications: prevention of osteoporotic hip fracture, bone tumor therapy, spinal fusion.

R.11.5
11:55
Authors : Lucio Litti (a), Niccolò Rivato (a), Marina Gobbo (a), Alfonso Venzo (a), Giulio Fracasso (b), Pasquina Marzola (b), Marco Colombatti (b), Moreno Meneghetti (a)
Affiliations : (a) Department of Chemical Sciences, University of Padova, Padova, Italy; (b) Department of Pathology and Diagnostics, University of Verona, Verona, Italy

Resume : Multimodal contrast agents (MCAs) exploit the benefit of multiple and complementary imaging techniques. Magnetic resonance imaging uses safe radiation and allows total body screening, but suffers on low spatial resolution if compared to optical imaging, that is characterized, however, by low tissue penetration. Surface Enhanced Raman Spectroscopy (SERS) is a vibrational technique amplified by a plasmonic substrates, namely noble metal nanoparticles. SERS allows imaging at sub-micrometer resolution with intensities comparable to fluorescence. Into this context we designed the synthesis of SuperDOTA, a new polyethylene glycol based polymer characterized by high Gd3+ loadings. SuperDOTA consists by three main fractions. The first is a cysteine amino acid, containing a thiol group for a stable linking to AuNPs surfaces. The second is a repetition of a short PEG spacer and a DOTA based branch for the Gd3+ chelation. The third is a long-chain PEG, to enhance the biocompatibility. Gold nanoparticles were synthesized by laser ablation synthesis in solvent (LASiS) and a SERS substrate is obtained by a controlled centrifugation. Si-Naphthalocyanine, used as SERS label, was functionalized with mercaptoethanol on both the apical sites to improve the optimal situation in which the dye molecule stays between two plasmonic particles, i.e. in a hot spot. The new nanostructure is used for multicontrast imaging using both MRI and SERS also for in-vivo measurements.

R.11.6
12:10
Authors : C. Zafiu1, M. Hülsemann1, K. Kühbach1, Y. Herrmann1, L. Peters1, C. Linnartz1, K. Kravchenko1, A. Kulawik1, T. Bujnicki1,2, J. Willbold1, O. Bannach1,2 and D. Willbold1,2
Affiliations : 1Forschungszentrum Jülich, ICS-6 Structural Biochemistry, 52428 Jülich, Germany 2Heinrich-Heine-University, Institut für Physikalische Biologie Universitätsstraße 1 40225 Düsseldorf, Germany

Resume : A reliable preclinical diagnosis of neurodegenerative diseases, such as Alzheimer’s disease (AD), is of great importance both for drug development and efficient treatment. Immunoassays are widely used for multiple sample analysis and quantification of biomarkers in biological samples. A promising biomarker for AD is the Amyloid beta (Abeta) oligomer, an aggregated but soluble multimeric form of the Abeta peptide which is the major culprit in AD pathology. Such oligomers can be detected by the sFIDA (surface-based fluorescence intensity distribution analysis) assay. A unique feature of the sFIDA assay is its ability not only to count single oligomers but also to analyze the composition of each particle. Therefore also hetero-aggregates consisting of more than one disease-associated peptide can be quantified. In this work we present a set of standard materials that can be used in oligomer-specific immunoassays. In contrast to other materials developed for oligomer-specific diagnostics the presented materials are tunable in their number of epitopes and epitope composition. A tunable epitope quantity and composition allows the design of hetero-aggregate mimicking particles in the oligomer size range. Therefore, immunoassay development and standardization can be performed towards the detection and quantification of hetero-aggregates within biological samples. We present the synthesis strategy of the nanoparticles and show the performance of these materials in the nanoparticle sensitive sFIDA assay on the example of hetero-aggregates consisting of Abeta and Tau protein.

R.11.7
12:25 Lunch break    
 
Hyperthermia - COST RADIOMAG : Nguyen TK Thanh- B. Kalska-Szostko - C. Sangregorio - S. Begin
13:30
Authors : Daniel Ortega, Simo Spassov, RADIOMAG-TEAM
Affiliations : Madrid Institute for Advanced Studies in Nanoscience (IMDEA Nanociencia), Madrid, Spain; Royal Meteorological Institute of Belgium; 131 researchers from 24 countries (http://www.cost-radiomag.eu/)

Resume : Cancer is a leading cause of death worldwide [1]. Future projections predict globally an increase up to 23.6 million new cases each year by 2030. Therefore, cancer research cannot wait, and new approaches are urgently required. RADIOMAG aims at building up the next generation of researchers in a highly multidisciplinary field by enabling current and organising new research dealing with the efficiency of radiotherapy and its synergetic combination with magnetic fluid hyperthermia (MFH). The latter treatment takes advantage of the heat produced by magnetic particles in alternating magnetic fields to kill or damage cancer cells [2]. The last two decades have been quite prolific in the development of bespoke magnetic nanoparticles and instrumentation for MFH [3], but despite the recent positive outcomes from clinical trials with glioblastoma multiforme patients, the treatment is still far from becoming a standard practice. The presentation will give an overview about the activities of this COST Action and present early scientific results. Special emphasis will be put on the design of a large scale inter-laboratory experiment, the first of its kind in the pursuit of a more accurate and comparable characterisation of nanoparticles for magnetic fluid hyperthermia. 1. S.W. Bernard, WHO World Cancer Report, ISBN 978-92-832-0429-9, (2014) 2. A. Hervault et al, Nanoscale 6 (2014) 11553; S. Dutz, R. Hergtet al, Nanotechnology 25 (2014) 452001 3. E. Périgo et al, Appl. Phys. Rev. 2 (2015) 041302

R.12.1
13:50
Authors : Gauvin Hemery, Sarah MacEwan, Ashutosh Chilkoti, Sébastien Lecommandoux, Elisabeth Garanger, Olivier Sandre
Affiliations : LCPO Univ. Bordeaux / CNRS / Bordeaux-INP, ENSCBP 16 Avenue Pey Berland, 33607 Pessac, France; Department of Biomedical Engineering, Duke University, Campus Box 90281, Durham, North Carolina 27708, USA

Resume : Elastin-like proteins (ELP) are recombinant proteins of the VPGXG pentapeptide (X being any amino acid but proline), the sequence of elastin, an extracellular matrix protein that undergoes deswelling transition at a critical temperature. This communication reports the grafting of diblock ELPs designed with a thermosensitive block and a hydrophilic block proving steric repulsion, onto superparamagnetic iron oxide NPs. Magnetic cores of superior magnetic heating efficiency were prepared by the DEG-NMDEA route introduced by Caruntu et al. The functionalization of the magnetic NPs by mixed brushes of ELP and PEO chains resulted into stable magnetic and thermosensitive colloids with a decreasing temperature-size response. The ELP and PEO grafting was achieved by a convergent strategy using a phosphonate moiety introduced by a crosslinking agent grafted onto a cysteine residue near the N-terminus of the diblock ELP construction or on PEG-SH. In situ DLS measurements during magnetic hyperthermia (MH) indicated that diblock ELP-grafted iron oxide NPs exhibited fast size changes versus the applied field strength profile. At long times (thermal equilibrium), the brush thickness correlates with the macroscopic temperature measured by fiber optic thermometry. During the MH treatment, a transient gap between the macroscopic and the local temperature was also evidenced. These results could help understanding the ?cold hyperthermia? effect of iron oxide NPs in intra-cellular compartments.

R.12.2
14:10
Authors : Caroline Thébault, Grégory Ramniceanu, Johanne Seguin, Claire Beauvineau, Christian Girard, Nathalie Mignet, Christine Ménager, Bich-Thuy Doan
Affiliations : Caroline Thébault Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire PHENIX, Case 51, 4 place Jussieu, F-75005 Paris, France ; Grégory Ramniceanu Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France; Johanne Seguin Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France; Claire Beauvineau Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France; Christian Girard Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France; Nathalie Mignet Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France; Christine Ménager Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire PHENIX, Case 51, 4 place Jussieu, F-75005 Paris, France ; Bich-Thuy Doan Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, F-75006 Paris, France;

Resume : Theranostic systems are developed to monitor a treatment in vivo according to their abilities for both imaging and therapy. We propose an innovative strategy to treat colon cancer with the design of magnetic thermosensitive liposomes that enable to target a superficial tumor under a magnetic field gradient and simultaneously to deliver an antitumoral drug by High Intensity Focused Ultrasounds (HIFU) application, with additional bimodal imaging properties for in vivo monitoring. In our study, we demonstrate the significant increase of accumulation of Ultra-Magnetic Liposomes (UML) in CT26 murine tumor using magnetic guidance compared with passive enhanced permeability retention effect. UMLs are highly loaded with magnetic nanoparticles of iron oxide (γ-Fe2O3) enabling both magnetic guidance and in vivo monitoring by MRI. The addition of a fluorescent probe in the formulation allows to track them by optical imaging. In vivo UML biodistribution was evaluated with dynamic susceptibility contrast imaging in MRI and fluorescent imaging. The accumulation of UMLs into the tumor after I.V. injection was measured using MRI image percentile processing, iron dosage by ICP AES and histology. Co-encapsulation of magnetic nanoparticles and SN38, an antitumoral drug, gave theranostic properties to our thermosensitive liposomes. Application of HIFU can, then, be used in the tumor for an active release of the drug in the region of interest for the development of an innovative therapy.

R.12.4
14:25
Authors : Cristina Blanco-Andujar1, S. Begin-Colin, Pauline Bonazza2, Claire Billotey2, Delphine Felder1
Affiliations : (1) Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), UMR-7504 CNRS-Université de Strasbourg, 23 rue du Loess, BP 34, 67034 Strasbourg Cedex 2, France (2) PU-PH Biophysique -Médecine Nucléaire, EMR 3738- UCBL-HCL-UJM, Plateforme IMTHERNAT, Hôpital Edouard Herriot, 5 place d?Arsonval, 69437 Lyon Cedex 3

Resume : Despite the use of combined therapies for the treatment of colorectal metastatic cancer (CRC), the expected survival upon treatment is still less than 8 months. These devastating numbers only prove the necessity of developing new strategies to treat this aggressive disease. Magnetic iron oxide nanoparticles (IONPs) are an attractive platform for the development of targeted therapies. These particles can not only be used as passive agents for magnetic resonance imaging but also as active therapeutic tools in drug delivery or magnetic hyperthermia. The latter has gained great attention for the treatment of malignant tissue due to the possibility of limiting the treated area and enhancing drug efficiency. Herein, 10-30 nm IONPs with different magnetic anisotropies were synthesised and coated with multifunctional dendrons,[1] leading to highly stable colloidal suspensions under physiological relevant conditions. More importantly, their heat loss capability and relaxivity were highly dependent on particle anisotropy leading to values superior to those exhibited by commercial available formulations. Cell response was studied as a function of NP coating, concentration and morphology, as well as under MH treatment. Finally, preliminary in vivo results on the distribution of these NPs in tumour models will be presented. To summarise, we have developed a synthesis and functionalisation method yielding stable dendronised-IONPs suspensions. This nanoplatform has the potential to fulfil the need for a new theranostic tool for the treatment of colorectal and other cancers due to its stability and therapeutic properties. References 1. Walter, A., et al., Chem. Mat., 2014. 26(18): p. 5252-5264.

R.12.5
14:40
Authors : Lilin Wang, Kuan Boone Tan, Nguyen T. K. Thanh*
Affiliations : Biophysics group, Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT, UCL Healthcare Biomagnetics and Nanomaterials Laboratories, 21 Albemarle Street, London W1S 4BS http://www.ntk-thanh.co.uk, Email: ntk.thanh@ucl.co.uk

Resume : Key words: Magnetic nanoparticle; Liposome; drug combination; Magnetic nanoparticles have been widely investigated as a promising nano-medicine agent since last decade. A number of in vitro and in vivo results suggest the chemo-thermotherapy via multifunctional magnetic nanoparticle has positive effect in cancer treatment [1]. However, unlike the thermo-radiotherapy, the clinical trials of chemo-thermotherapy could not make a consistent synergism conclusion. [2] Apart from the complicated tumor architecture, it may due to the tumour heterogeneity. Herein, our group constructs a multifunctional magnetic thermo sensitive liposome and optimizes it by introducing both pharmaceutics and biomolecular concepts. In the first part, we refined the polyol method for synthesis the multi core magnetic nano-flower that has high magnetic property. In order to boost the chemo-thermo effect, the most synergistic chemodrugs combination ratio was carefully chosen among the 3 most prevalent anti breast cancer medicines: gemcitabine, paclitaxel and doxorubicin, by testing on different breast cancer cell lines. Both of them were loaded into the thermosensitve liposomes via thin film hydration methods. The efficiency of the multifunctional magnetic chemosensitive liposome will be verified and compared with the baseline among all cell lines. Based on the outcomes, the second part will be focusing on further optimizing our chemo-thermotherapy strategy via biomolecular analysis. Ref: [1] A. Hervault and N. T. K. Thanh, ?Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer,? Nanoscale, vol. 6, no. 20, pp. 11553?11573, 2014. [2] B. Hildebrandt, P. Wust, O. Ahlers, A. Dieing, G. Sreenivasa, T. Kerner, R. Felix, and H. Riess, ?The cellular and molecular basis of hyperthermia,? vol. 43, pp. 33?56, 2002

R.12.6
14:55
Authors : Laurence Motte
Affiliations : Inserm, U1148, Laboratory for Vascular Translational Science, Université Paris 13, Sorbonne Paris Cité, F-93017 Bobigny, France

Resume : Oligonucleotides (ODNs) present a high therapeutic potential for a wide variety of diseases. However, their clinical development is limited by their degradation by nucleases and their poor blood circulation time. Depending on the administration mode and the cellular target, these macromolecules will have to cross the vascular endothelium, to diffuse through the extracellular matrix, to be transport through the cell membrane and finally to reach the cytoplasm. To overcome these barriers, many strategies have been developed. Here, we report a method allowing the direct and one-step oligonucleotide conjugation onto iron oxide nanoparticle surface using complexation affinity of phosphate1,2 or phosphorothioate3 functions and avidity effect induced by the large number of these moieties on the ODN backbone for the nanoparticle surface. We show that the average number of ODN per nanoparticle could be controlled and that the adopted conformation was related to the grafting density progressing from a flat conformation to perpendicular one with the increase of ODN loading The phosphodiester ODN delivery in cells and the biological activity (inhibition of the nuclear localization of the transcription factor STAT3) seems to be related to the grafting density. Finally, we explore different strategies, based on the electrostatic interactions between the different partners, to functionalize the surface of SPIONs with a ODN and a cationic cell penetrating peptide3. References 1- Easily Controlled Grafting of Oligonucleotides on Fe2O3 Nanoparticles: Physico-Chemical Characterization of DNA Organization and Biological Activity Studies. F. Geinguenaud, I. Souissi, R.Fagard, Y. Lalatonne, L. Motte, J. Phys Chem. B 2014,1535-1544. 2- Electrostatic Assembly of a DNA Superparamagnetic Nanotool for Simultaneous Intracellular Delivery and In-Situ Monitoring, F. Geinguenaud, I. Souissi, R. Fagard, L. Motte, Y. Lalatonne, Nanomed. Nanotechnol., 8 (7), 2012,1106-15. 3- Iron oxide nanoparticles coated with a phosphorothioate oligonucleotide and a cationic peptide: exploring four different ways of surface functionalization. F. Geinguenaud, C. Banissi, A. Carpentier, L. Motte, Nanomaterials, Special Issue "Nanoparticles in Theranostics": invited article,5(4), 2015,1588-1609.

R.12.7
15:15 Coffee break    
15:35
Authors : Etelka Tombácz, Márta Szekeres, Erzsébet Illés, Ildikó Y. Tóth
Affiliations : Department of Physical Chemistry and Materials Science, University of Szeged, Aradivt 1, 6720 Szeged, Hungary

Resume : Biomedical applications of superparamagnetic iron oxide nanoparticles (SPIONs) require an optimized coating via which SPIONs interact with any biological entities (e.g., proteins, cell membranes). We demonstrate a spontaneous one-step way to form carboxylated/PEGylated shell on SPIONs by post-coating method, in which optimized magnetic cores were combined with commercial (e.g. poly(acrylic acid) and designed polymer molecules. In the latter, poly(ethylene glycol) methyl ether methacrylate (PEGMA) and acrylic acid (AA) were chemically coupled in a comb-like copolymer, P(PEGMA-co-AA) with PEG chains and pendant carboxylates in a single coating molecule. The multiple bindings on SPIONs via surface complexation of Fe-OH sites by carboxylates are spontaneous. The formed polyelectrolyte layer hinders SPIONs’ dissolution, provides combined electrostatic and steric (electrosteric) stabilization, and high protein repellency by PEG moieties. In addition, free carboxylates still exist in the shell for anchoring bioactive molecules via peptide bonding. In the lecture, we will show the synthesis and post-coating of naked SPIONs, their physicochemical and colloidal characterization and the comparison of optimized products’ testing for hemocompatibility (blood sedimentation rate, blood smear and blood cell viability), in vitro cell tests (MTT cell proliferation assay, Prussian blue staining), MRI contrast and hyperthermia efficiency.

R.12.8
15:55
Authors : Hong Liu, Jichuan Qiu, Baojin Ma, Shan Zhang
Affiliations : State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China

Resume : For tissue repair of regeneration based on tissue engineering principle, scientists with medical and biological background often pay much attention to stem cell itself, or use some traditional biomaterials as scaffold, and other researchers from materials engineering filed often pay much attention to scaffold research and the last step, test repairing effect in an animal model by implant the scaffold. The most important part, interaction between the surface of biomaterials and differentiation of stem cells is often ignored, because it need interdiscipline background, and people rarely possesses very strong background in both biology and materials science. Fortunately, most recently, an increasing number of researchers devote to this field, and pay much attention to the relationship between materials and stem cells, which will make great progress in this field. The effect of nanotopography of the biomaterials on differentiation of stem cells is the first topic to study the interaction between materials and stem cells. However, most researches were taken the materials such as silicon, PDMS as basic materials, because they are very easy for building nanostructures by micro-manufacture techniques. Although these works uncovered some unknown phenomenon about the response of stem cells on nanotopography, they are very far for application in tissue engineering because of the composition difference among the experimental samples and biomaterials. Nanoparticles, a very important category of biomaterials, have been widely investigated and even applied in cell and tissue imaging, drug delivery, photothermal cancer therapy, etc. Normally, the nanoparticles should be injected into the body for their therapy function. After fulfilling their bio-function, the nanoparticles, especially the particles without bio-degradation ability will stay in the body. Some of the nanoparticles can be discharged thorough circulatory system, and others may enter the area of the stem cells. As is well known, stem cells has strong Recent years, the interaction between material and stem cell has been attract much attention, because it is helpful to understand some bio-process and very useful for design and preparation of tissue engineering scaffold for tissue repair and tissue regeneration. Nanotopography is one of the most important physical cues for regulation fate of stem cells. Because the extracellular matrix is composed by polysaccharide and protein fibers with nanoscale diameter, the nanotopography can be act as a physical signal to tune differentiation of stem cells by endocytosis ability, which can take a large number of nanoparticles. Although there are thousands researchers do research on the interaction between cancer cell and nanoparticles, a few scientists have involved in the effect of nanoparticle on differentiation of stem cells. However, the behavior of nanoparticles in stem cell is very important, which could affect the differentiation ability of the stem cell, and will further affect the maintain and reconstruction of some important tissues in the body. Therefore, the regulation effect of nanoparticles on differentiation of stem cells is a very important topic for biomaterials. With last three years, our group focuses on the interaction of nanostructures and nanoparticles and stem cells. We found some nanoarray and nanostructures built by biomaterials can enhance osteogenic and neural differentiation, and demonstrates that the localized and committed differentiation could be realized in one system by integrating materials with different topography. Moreover, we have found that some nanoparticles, such as graphene quantum dots, lithium niobate nanoparticle, not only have good cytocompatibility, but also can enhance osteogenic differentiation of MSCs, which proved the safety of some nanoparticles during the therapy applications. In this talk, we will report the above works, and try to explain the reasons for physical signal induced differentiation from both physical mechanism and bio pathways. We believe that the regulation effect of nanostructures and nanoparticle will have great impact for design and application of biomaterials, especially for tissue engineering scaffold, and will bring great progress in tissue regeneration medicine.

R.12.9
16:10
Authors : Urszula Klekotka1, Dariusz Satua2, Beata Kalska-Szostko 1
Affiliations : University of Bialystok, Institute of Chemistry, Ciolkowskiego 1K, 15-245 Bialystok, Poland1* University of Bialystok, Department of Physics, Ciolkowskiego 1L 15-245 Bialystok, Poland2

Resume : Nowadays, nanoparticles can be obtained by many various methods in variable forms. At the nanometric level properties of nanostructures are very sensitive to many parameters: composition, size, crystallinity, shape. In this presentation we would like to compare nanoparticles which were prepared by three methods. Chosen samples were fabricated by: i) co-percipitation of magnetite from iron chlorides in aqueous solution, ii) thermal decomposition of iron (III) acetylacetonate comples in organic solution; iii) laser ablation in solution. Each of the presented methods leads to other kind of ferrofluids and therefore its application is different. Laser Ablation Synthesis in Solution, involves few phenomena: firstly material is evaporated from bulk target, with use of focused lasers short impulses, melt reactions, and particles fabrication. By this method, bimetallic, but also metal oxide nanoparticles can be obtained. Chemical synthesis of nanoparticles in organic or inorganic solvent and proper stabilizer allows to ferrofluid fabrication. Every type of obtained nanoparticles will be characterized by TEM, IR, XRD, UV-Vis and Mössbauer spectroscopy.

R.12.10
16:25
Authors : C. Tudisco,1,2, M. T. Cambria,3, A.E. Giuffrida,1,2 F. Sinatra,3, A. Alba,3, C. D. Anfuso,3, G. Lupo,3, A. Falanga,4, S. Galdiero,4, C. Satriano,1, G. G. Condorelli,1,2,*
Affiliations : 1 Dipartimento di Scienze Chimiche, Università di Catania, 95125 Catania, Italy; 2 INSTM UdR di Catania, 95125 Catania, Italy; 3 Dipartimento di Scienze Biomediche e Biotecnologiche, Università di Catania, 95100 Catania,Italy; 4 Dipartimento di Farmacia, Università di Napoli “Federico II”, 80134, Napoli, Italy.

Resume : The hybrid organic/inorganic nature of the surface of functionalized magnetic iron nanoparticles (MNPs) plays a pivotal role in determining their properties and in turn their applicability. In this contribution, the role of Fe3O4 - surface functionalization on MNPs capability of overcoming “in vitro” models of the blood-brain barrier (BBB) has been investigated. Three different coatings have been covalently anchored on the Fe3O4 surface through a multistep route based on MNPs prefunctionalization with a bifunctional phosphonic linker, (3-aminopropyl) phosphonic acid, able to bind on iron surface through the phosphonic groups. Then the functional molecules have been covalently bonded to the amino group of the phosphonic monolayer. In particular, attention has been focused on three functional systems: a simple polyethylene glycol (PEG) coating, a mixed folic acid – PEG layer and a coating based on gH625 a viral fusion peptide able to easily cross through the cell membrane. To monitor MNPs uptake into BBB, all the nanosystems have been marked with rhodamine- or NBD- based luminescent probes covalently bonded, respectively, to the phosphonic acid pre-functionalized nanoparticles or to the anchored gH625 peptide. Finally, using primary microvascular endothelial cells from human brain (EC), the effect of MNPs permeation on the production of reactive oxygen species (ROS) has been evaluated and compared for all the investigated nanosystems.

R.12.11
16:40
Authors : Donatella Vecchione 1,2 Paolo Antonio Netti 1,2,3 Enza Torino 2,3
Affiliations : 1 Department of Chemical Engineering, Materials and Industrial Production, University of Naples Federico II, Naples 80125, Italy 2 Istituto Italiano di Tecnologia, Center for Advanced Biomaterials for Healthcare IIT@CRIB, Naples 80125, Italy 3 Interdisciplinary Research Center on Biomaterials, University of Naples Federico II, Naples 80125, Italy

Resume : An early and effective diagnosis can increase even chances of survival that ensuring patients receive the most appropriate treatment. Nowadays diagnostic technologies could have a huge impact in the diagnosis and, therefore, in the clinical management of the pathologies at the early stages. In this context, the integrated PET/MRI plays a key role using sequentially acquired data that allows both spatial and temporal correlation of the signals. The aim of this work is the production of core-shell polymeric nanoparticles obtained by a complex coacervation method for theranostic and dual imaging applications. An accurate control of the coacervation steps is realized by modulating the miscibility gap through the use of temperature, allowing the formation of a nanovector that provide both MRI and PET modalities and, at the same time, reduce side effects and improve strongly the quality of the obtained images. The obtained chitosan/hyaluronic acid nanostructures are stabilized by a double crosslinking able to retain active compounds. The impact of the hydrophilic properties of the hydrogel matrix on the enhancement of the relaxivity of the Gd-DTPA is evaluated, while sorption of FDG into the polymeric matrix is discussed in terms of activity of the radiotracers and changes in metabolic pathways due to encapsulation. Results investigate the combined effect of both tracers and evaluate the quality of the signal intensity in vitro and in vivo.

R.12.12

No abstract for this day


Symposium organizers
Beata KALSKA-SZOSTKOUniversity of Bialystok

Institut of Chemistry Hurtowa 1 15-399 Bialystok Poland

+48 857457814
kalska@uwb.edu.pl
Claudio SANGREGORIOCNR- ICCOM

via Madonna del piano 10 50019 Sesto Fiorentino (Firenze) Italy

+39 0554573270
csangregorio@iccom.cnr.it
Nguyen TK THANHUniversity College London

Biophysics Group Department of Physics and Astronomy http://www.ntk-thanh.co.uk

+44 2074916509
ntk.thanh@ucl.ac.uk
Sylvie BEGIN-COLINInstitut of Physic and Chemistry of Materials of Strasbourg

IPCMS UMR CNRS Unistra 7504, BP43, 67034 Strasbourg cedex, France

sylvie.begin@ipcms.unistra.fr