Engineering Discoidal Polymeric Nanoconstructs for the Multi-Physics Treatment of Brain Tumors

Cel

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.

Dziedzina nauki

System finansowania

ERC-CG - ERC Consolidator Grants

Instytucja przyjmująca

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA

Wkład UE

€ 2 390 000,00

Adres

VIA MOREGO 30
16163 Genova
Włochy

Region

Nord-Ovest Liguria Genova

Rodzaj działalności

Research Organisations

Kontakt administracyjny

Gabriele Ballero (Mr.)

Kierownik naukowy

Paolo Decuzzi (Prof.)

Linki

Kontakt z organizacją Strona internetowa

Koszt całkowity

Brak danych

Beneficjenci (1)