Objectif Despite significant advances in chemotherapy, the effective treatment of malignant masses via systemically injectable agents are still limited by insufficient accumulation at the biological target (<< 10% injected dose per gram tumor) and non-specific sequestration by the reticulo-endothelial system (tumor/liver < 0.1).The goal of this proposal is to engineer Discoidal Polymeric Nanoconstructs (DPNs) to preferentially target the malignant neovasculature for the delivery of imaging agents, controlled release of therapeutic molecules and thermal energy. The central hypothesis is that the size, shape, surface properties and stiffness (4S parameters) of the DPNs can be controlled during synthesis, and that therapeutic molecules (Temozolomide), Gd(DOTA) complexes and ultra-small Super-Paramagnetic Iron Oxide nanoparticles (USPIOs) can be efficiently incorporated within the DPN polymeric matrix.This will be achieved by pursuing 3 specific aims: i) synthesis and physico-chemical characterization of poly(lactic-co-glycolic acid)/poly(ethylene glycol) DPNs with multiple 4S combinations; ii) in-silico and in vitro rational selection of DPN configurations with preferential tumor deposition, low macrophage uptake and high loading; and iii) in-vivo testing of the DPN imaging and therapeutic performance in mice bearing Glioblastoma Multiforme (GBM).The innovation stays in i) using synergistically three different targeting strategies (rational selection of the 4S parameters; magnetic guidance via external magnets acting on the USPIOs; specific ligand-receptor recognition of the tumor neovasculature); ii) combining therapeutic and imaging molecules within the same nanoconstruct; and iii) employing synergistically different therapeutic approaches (molecular and thermal ablation therapies). This would allow us to support minimally invasive screening via clinical imaging and enhance therapeutic efficacy in GBM patients. Champ scientifique engineering and technologynanotechnologynano-materialsnatural scienceschemical sciencesorganic chemistryaliphatic compoundsnatural sciencescomputer and information sciencescomputational sciencemultiphysics Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-CG-2013-PE8 - ERC Consolidator Grant - Products and Processes Engineering Appel à propositions ERC-2013-CoG Voir d’autres projets de cet appel Régime de financement ERC-CG - ERC Consolidator Grants Institution d’accueil FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Contribution de l’UE € 2 390 000,00 Adresse VIA MOREGO 30 16163 Genova Italie Voir sur la carte Région Nord-Ovest Liguria Genova Type d’activité Research Organisations Contact administratif Gabriele Ballero (Mr.) Chercheur principal Paolo Decuzzi (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Italie Contribution de l’UE € 2 390 000,00 Adresse VIA MOREGO 30 16163 Genova Voir sur la carte Région Nord-Ovest Liguria Genova Type d’activité Research Organisations Contact administratif Gabriele Ballero (Mr.) Chercheur principal Paolo Decuzzi (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée