UPR 5301

Simon Coninx thesis defense on October 24th, 2022

Simon Coninx completed his thesis at Cermav under the supervision of Rachel Auzely, Professor at Université Grenoble Alpes. It is entitled "Nanogels based on boron-rich glycosaminoglycans for the multi-modal treatment of cancer". Click on the title for more information.

Abstract :

“The derivatives currently used for boron neutron capture therapy (BNCT) have shown some limitations. Actually, only BPA and BSH are clinically accepted and difficulties concerning their selectivity towards the tumor, their follow-up by imaging after injection as well as the amount of boron accumulated in tumors have been identified and do not allow an optimum treatment efficiency. Nanocarriers appear to be a promising solution to meet these needs because they have many advantages, in particular the possibility to encapsulate boron-rich molecules such as sodium borocaptate (BSH), to co-encapsulate an imaging traceable molecule or active in chemotherapy, and to improve tumor targeting thanks to specific ligands in addition to passive accumulation (EPR effect, enhanced permeability and retention). In this perspective, polysaccharide nanogels appear as prime candidates because they also have all the properties of a hydrogel, i.e. they are flexible, modulable, water-soluble and form a physical or chemical cross-linked network to limit rapid degradation by enzymes or the liver. In this project, the strategy consisted in synthesizing biocompatible and biodegradable thermosensitive nanogels based on hyaluronic acid (HA) or heparosan (Hep) for BNCT. Thus, thermosensitive monomers have been grafted onto polysaccharides by different methods. The most advanced technique using vinylsulfone has made possible the formation of crosslinked nanogels that are stable at room temperature. The encapsulation of BODIPY-BSH in high proportions allowed on one hand to monitor these nanocarriers by fluorescence, and on the other hand to transport boron in large quantities. Biological tests have shown the absence of toxicity and strong uptake by tumor cells in vitro. Concerning in vivo experiments, some of the nanogels accumulate in the tumor but the majority of them accumulate in the liver, certainly due to their sizes and their high polydispersity index (PDI). Finally, in order to further increase the amount of boron in the nanocarriers, the study of other thermosensitive polymers is proposed for the grafting of cyclodextrins (CD) on the surface and the encapsulation of BODIPY-BSH. The final objective is therefore the formation of new nanogels enriched in CD and containing an even higher proportion of boron for increased efficiency in BNCT.”