TThe ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24–25, 2015. Workshop Report

This report summarizes the results of the 3rd Joint ENCCA-WP7, EuroSarc, EEC, PROVABES, and EURAMOS European Bone Sarcoma Network Meeting, which was held at the Children's Cancer Research Institute in Vienna, Austria on September 24-25, 2015. The joint bone sarcoma network meetings bring together European bone sarcoma researchers to present and discuss current knowledge on bone sarcoma biology, genetics, immunology, as well as results from preclinical investigations and clinical trials, to generate novel hypotheses for collaborative biological and clinical investigations. The ultimate goal is to further improve therapy and outcome in patients with bone sarcomas

Chemical nanosensors based on molecularly imprinted polymer nanocomposites synthetized by controlled radical polymerisation

Les polymères à empreintes moléculaires (MIP, pour molecularly imprinted polymers en anglais) sont des récepteurs synthétiques, parfois appelés "anticorps en plastique", capables de reconnaitre et fixer spécifiquement une molécule cible. L impression moléculaire s est imposée, durant les trente dernières années, comme une technique pour la synthèse des structures réticulées possédant une remarquable affinité et sélectivité vis-à-vis d une espèce chimique utilisée comme molécule empreinte dans un procédé de moulage au niveau moléculaire. La grande variété de matériaux et de formats accessibles à cette technique lui ont permis de trouver un grand nombre d applications, telles que la séparation, les capteurs, la catalyse, le ré-largage contrôlé de médicaments. Depuis leur apparition, la plupart des MIPs a été synthétisée par polymérisation radicalaire libre (FRP) des monomères vinyliques. Cette méthode de polymérisation représente un excellent choix en termes de simplicité de mise en place, tolérance par rapport aux solvants et aux différents groupements fonctionnels des ingrédients. Cependant, plusieurs désavantages liés à cette technique limitent la possibilité d obtenir un contrôle adéquate vis-à-vis de certaines caractéristiques fondamentales pour des applications en nano-technologies. L introduction des techniques de polymérisation radicalaire contrôlée/vivante (CRP) a donc représentée une avancée importante et a permis de dépasser certains limites associés aux MIPs synthétisés par FRP. Dans ce contexte, ce travail de thèse a étudié les avantages provenant de l utilisation d'une méthode CRP, le RAFT, pour la synthèse des MIP. Ce travail a été mené en se focalisant sur les caractéristiques principales des CRPs : le caractère vivant et, en même temps, contrôlé. Dans un premier temps, nous avons utilisé l aspect vivant de la polymérisation pour la synthèse des nanocomposites MIP, possédant des propriétés superparamagnétiques. Celle-ci a été effectuée par polymérisation de couches p(EGDMA-co-MAA) par RAFT amorcée à la surface des particules de Fe3O4 préfonctionnalisées avec des groupements amine. Le greffage de ces couches a été obtenu en employant des ultrasons comme source d'agitation, et en testant différents solvants pour en apprécier l influence sur la structure et la morphologie des composites résultants. Nous avons démontré que le greffage se produit d une façon homogène, et que grâce au caractère vivant de la polymérisation RAFT, les composites peuvent être fonctionnalisés davantage, par exemple par des chaines p(EGMP), pour ajuster leur propriétés de surface. Dans un deuxième temps, nous nous sommes consacrés à une étude comparative visant la mise en évidence des avantages de la RAFT par rapport à la FRP en termes de performances des MIP acryliques et méthacryliques. Pour mieux apprécier les différences induites par la méthode de polymérisation, le dégrée de réticulation et donc la flexibilité des réseaux ont été variés de façon systématique. Cette stratégie a permis de bien apprécier les différences induites par chaque technique de polymérisation. Les résultats ont démontré que la RAFT permet de synthétiser des MIPs ayant une meilleure affinité pour leur molécule cible, et que cette amélioration est due à une distribution plus homogène des points de réticulation au sein du réseau. Finalement, nous avons appliqué la RAFT pour la synthèse de nanocapteurs individuels basés sur des composite MIP intégrant des nanoparticules d'or, et utilisant la spectroscopie Raman exaltée (SERS) pour la détection.Molecularly imprinted polymers (MIPs) are synthetic receptors, also known as antibody mimics, that can specifically bind target molecules. Molecular imprinting has emerged, over the last 30 years; it is an extremely versatile strategy for synthesizing networks possessing high affinity and selectivity for a chemical species, used as a molecular template during their synthesis. The wide variety of materials and formats that are accessible through this strategy has resulted in a broad spectrum of applications for such MIPs, ranging from separation to sensing, catalysis, drug delivery, etc. Since the beginning, the great majority of the imprinted networks has been synthesized by assembling vinyl monomers via free-radical polymerization (FRP). This polymerization method represents a convenient choice for synthesizing MIPs, due to its easy setup, versatility, tolerance with respect to many solvents and functional groups. However, some drawbacks greatly affect the possibility of achieving of suitable degree of control over some polymeric parameters which become important for specific applications. The introduction of controlled/ living radical polymerization (CRP) techniques has then represented an opportunity for MIPs to reduce, and in some cases even to overcome, some of their limits arising from FRP. In this respect, this Ph.D. thesis has studied how the use of RAFT polymerization, one of the most applied CRPs, can be advantageously used to syntheze MIPs. This has been done by focusing on the main characteristics of CRPs: their living and controlled nature. The living nature has been exploited during the first part of this work, which involved the synthesis of superparamagnetic molecularly imprinted nanocomposites via surface-initiated RAFT polymerization of p(EGDMA-co-MAA) on amino-modified Fe3O4 nanoparticles. The polymer grafting has been performed using an unusual stirring technique (i.e. ultrasonication) during the polymerization step, and by testing different polymerization solvents for evaluating their effect on the composite structure. It has been observed that the grafting resulted in homogeneous polymer layers, the thickness of which could be controlled by adjusting the RAFT/radical source ratio. Moreover, the living nature of RAFT fragments has been exploited for post-functionalizing the surface of a composite particle with p(EGMP) brushes, thus demonstrating the potential of fine-tuning the particle surface properties through the living chain ends. In the second part of the thesis, an in-depth study has been performed on the effects induced by the use of controlled (RAFT) polymerization conditions on the binding behaviour and structural parameters of bulk acrylic and methacrylic MIPs and the corresponding non-imprinted polymers, synthesized by RAFT and FRP with varying cross-linking degree. This strategy actually provided scaffolds with progressively increased degree of flexibility (especially in the case of acrylics) which allowed visualize the enhancement of binding and structural differences arising from the polymerization technique. As a result, it has been observed that the use of controlled (RAFT) conditions induced, on the imprinted networks, an increased template affinity over equivalent FRPs, and it has been demonstrated that this improved affinity can be related to more homogeneous distributions of the cross-linking points achieved during RAFT polymerization. The third part presents preliminary results toward the synthesis by RAFT of individual multi-composite MIP nanosensors using enhanced Raman spectroscopy (SERS) for detection.COMPIEGNE-BU (601592101) / SudocSudocFranceF

An easy synthesis of small, stable and water-compatible superparamagnetic protein-specific molecularly imprinted nanoparticles

International audienceWe report the synthesis of small (below 100 nm), stable and water-compatible superparamagnetic molecularly imprinted nanocomposites using water-soluble, dithiocarbamate-based photoiniferters. These agents were adsorbed directly on the surface of maghemite nanoparticles and allowed the synthesis of thin layers of molecularly imprinted polymer able to specifically and selectively bind green fluorescent protein as a model protein. To the best or our knowledge, this is the first time that water soluble photoiniferters have been used to prepare this kind of imprinted materials

Magnetic molecularly imprinted polymer nanocomposites via surface-initiated RAFT polymerization

International audienceA general protocol to synthesize superparamagnetic molecularly imprinted polymer particles, using a RAFT-mediated approach, is described. S- propranolol-imprinted composites were obtained by functionalizing commercially available amino-modified Fe3O4 nanoparticles with a trithiocarbonate agent and subsequently by polymerizing thin molecularly imprinted layers. Different parameters were optimized and their effect on both nanomorphology and imprinting behaviour was studied. Optimum conditions allowed the synthesis of 40 nm composite particles with a 7 nm MIP shell, exhibiting superparamagnetic properties and specific molecular recognition of S- propranolol. The possibility of fine-tuning the surface properties of the particles is demonstrated by using the "living" nature of active RAFT fragments present on the surface of the composites to further functionalize the particles with ethylene glycol methacrylate phosphate polymer brushes

Molecularly Imprinted Polymers for Chemical Sensing: A Tutorial Review

International audienceThe field of molecularly imprinted polymer (MIP)-based chemosensors has been experiencing constant growth for several decades. Since the beginning, their continuous development has been driven by the need for simple devices with optimum selectivity for the detection of various compounds in fields such as medical diagnosis, environmental and industrial monitoring, food and toxicological analysis, and, more recently, the detection of traces of explosives or their precursors. This review presents an overview of the main research efforts made so far for the development of MIP-based chemosensors, critically discusses the pros and cons, and gives perspectives for further developments in this field. View Full-Tex

Photopolymerization and Photostructuring of Molecularly Imprinted Polymers

International audienceOver the past few decades, molecularly imprinted polymers (MIPs) have become extremely attractive materials for biomimetic molecular recognition due to their excellent affinity and specificity, combined with robustness, easy engineering, and competitive costs. MIPs are synthetic antibody mimics obtained by the synthesis of 3D polymer networks around template molecules, thus generating specific binding cavities. Numerous efforts have been made to improve the performances and the versatility of MIPs, with a special focus on ways to control their size, morphology, and physical form for a given application. Gaining control over these parameters has allowed MIPs to adopt a defined micro- and nanostructure, providing access to nanocomposites and micro/nanosystems, with fine-tuned properties, which become critical for modern applications ranging from chemical sensing to bioimaging and medical therapy. In this rich and complex context, light as a cheap and versatile source of energy has emerged as a powerful tool for structuring MIPs. This review presents the most recent advances on structuring MIPs at the nano/microscale, using light as a stimulus to trigger the polymerization process. Thus, after a general introduction on radical polymerization of MIPs, with a special emphasis on photopolymerization by UV and visible light, the reader will be presented with ways of structuring MIPs by processes that are inherently spatially confined, such as localized photopolymerization and lithographic techniques, supported by representative examples and complemented with a final outlook on future trends in this field

RACCONTARE PER IMMAGINI: IL PRIMO CINEMA DELLA STORIA (“OBIETTIVO” SUL PALEOLITICO)

Nell'ambito del programma MuSST - Musei e sviluppo dei sistemi territoriali, promosso dalla Direzione Generale Musei, il Polo Museale del Veneto ha individuato iniziative strategiche volte a consolidare il dialogo fra realtà pubbliche e private nell'ottica di una valorizzazione partecipat

A light-triggerable nanoparticle library for the controlled release of non-coding RNAs

RNA-based therapies offer a wide range of therapeutic interventions including for the treatment of skin diseases; however, the strategies to deliver efficiently these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we synthesized a triggerable polymeric nanoparticle (NP) library composed by 160 formulations, presenting physico-chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500%) than commercial Lipofectamine in gene knockdown activity. These formulations had differential internalization by skin cells and the endosomal escape was rapid (minutes range) as shown by the recruitment of galectin-8. The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA-150-5p healed faster than wounds treated with scramble miRNA. Light-activatable NPs offer a new strategy to deliver topically non-coding RNAs