Glioblastoma IDH1 WT, a grade IV malignant glioma, is one of the most aggressive and lethal cancer, with less than 7.2 % survival rates after 5 years. The current FDA-approved therapeutic approach is Gliadel®, a post-operative surgical implant. The latter presents some limitations and side effects, including the stiffness of the wafers and the lack of specificity of the carmustin cargo. NanoGlio aims at developing a post-surgical deposit, with mechanical properties adapted to the brain tissue, and loaded with drug-loaded nanoparticles targeting tumor cells. Elastin-like polypeptides (ELPs) are in particular used in this project as biocompatible, biodegradable, non-immunogenic and thermo-responsive polymer backbones. The polypeptide chain ends are conjugated on one side to verteporfin (VP, a FDA approved photosensitizer), and on the other side to glucose moieties. VP is used for Photo- or Radio- Dynamic Therapy (PDT/RDT), i.e. photochemical damage via ROS accumulation when activated by an IR laser or X-rays, leading to tumor cell apoptosis. Glucose confers cellular specificity to the resulting nanocarriers by targeting GLUT-1 transporters overexpressed in the blood brain barrier (BBB) and glioma cells. Resulting particles are loaded into a hydrogel and its drug release studied. In vitro and in vivo assays are performed in collaboration with BRIC (Inserm U1312) and IBGC (UMR5095).
Collaboration: BRIC – Inserm U1312 : Dr Charles Dupin, PU/PH Sandrine Dabernat, PU/PH Véronique Vendrely, PH Olivier Mollier IBGC - UMR5095 : Dr Thomas Daubon
Fundings: SIRIC BRIO CommuCan Cancéropole GSO FRM - Post-doctoral fellowship - SPF202110014243 Région Nouvelle Aquitaine