Soutenance de Thèse de Mme Heba ALNEMEH-AL ALI
The July 6, 2022
Development of a potential nano-based delivery system for cancer treatment
Directeur de Thèse: Mr Joël EYER
Glioblastoma (GBM) is a difficult-to-treat tumour that faces several challenges in the clinic. A peptide named NFL-TBS.40-63 (NFL-peptide) has been previously discovered in the laboratory and revealed its targeting properties against glioblastoma cells where it destroys their microtubules network inducing cell death. Here, we focused on the properties of this peptide and its coupling with other nanoparticles loaded or not with an anti-cancer drug. Our work demonstrated the ability of Biotinylated-NFL-peptide (BIOT-NFL-peptide) to form well-organized peptide nanofibers about 5 nm in diameter and several micrometres in length. We further explored the interaction between BIOT-NFL-nanofibers and other nanoparticles like gold nanoparticles and lipid nanocapsules, in the hope of using peptide-nanofibers as a vector to target the delivery of these particles into GBM. The presence of NFL-peptide-nanofibers alongside gold-nanoparticles showed an improvement in their internalization in GBM cells when treated with this conjugation (BIOT-NFL conjugated-gold nanoparticles) compared to gold-nanoparticles alone. BIOT-NFL-nanofibers have also been shown to fix lipid nanocapsules (LNCs), previously developed in our laboratory and used as carriers for anti-cancer drugs, all long the nanofiber. Lipid nanocapsules loaded with an anti-microtubule agent (Colchicine) have been developed in this study (Col-LNCs) and conjugated to the BIOT-NFL-peptide. A potential new nanosystem composed of BIOT-NFL-nanofibers decorated with lipid nanocapsules loaded with Colchicine was established, and then the in vitro cytotoxicity was analysed on rat GBM cells. Altogether, the self-assembled peptide nanofibers obtained from BIOT-NFL may represent promising GBM-targeting nanofibers that can be used to target the delivery of therapeutics into GBM cells.
