Objective 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. Fields of science 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) Topic(s) ERC-CG-2013-PE8 - ERC Consolidator Grant - Products and Processes Engineering Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Host institution FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA EU contribution € 2 390 000,00 Address VIA MOREGO 30 16163 Genova Italy See on map Region Nord-Ovest Liguria Genova Activity type Research Organisations Administrative Contact Gabriele Ballero (Mr.) Principal investigator Paolo Decuzzi (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Italy EU contribution € 2 390 000,00 Address VIA MOREGO 30 16163 Genova See on map Region Nord-Ovest Liguria Genova Activity type Research Organisations Administrative Contact Gabriele Ballero (Mr.) Principal investigator Paolo Decuzzi (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
