Works of our laboratory demonstrated that intermediate filaments, which are one of the three cytoskeleton elements, can bind tubulin dimers in specific sites named TBS (Tubulin-Binding Site). Some of these peptides corresponding to TBS sequences can inhibit in vitro tubulin polymerization in microtubules (MT). Works in this thesis consist of continuing the structural and functional characterization of these peptides. Thus, it has been possible to show that one of these peptides from vimentin protein, Vim-TBS.58-81, is able to enter in T98G human glioblastoma cells and to localize in the nucleus of the cells. When coupled to a pro-apoptotic peptide acting in the nuclear compartment, it is able to inhibit cell proliferation. Another peptide from the light neurofilament subunit, NFL-TBS.40-63, is able to enter in many glioma cell lines, to destabilize MT network and to inhibit cell proliferation and migration without affecting healthy cells of the brain (astrocytes and neurons). Injected by stereotaxy in the tumour of rat bearing F98 glioma, this peptide reduces glioma growth and stays localized in tumour tissue. A structural/functional analyze of this peptide highlights some secondary structures, β-sheet and α-helix. After grafting on lipid nanocapsules (LNC) surface, this peptide enhances their entrance in glioma cells in vitro and in vivo. Finally, LNC containing Paclitaxel or Ferrociphenol and grafted with NFL-TBS.40-63 peptide appeared to be more efficient to inhibit tumour growth in mice bearing GL261 glioma and in rat bearing 9L glioma respectively. All of this work presents new functions of targeting and cellular penetration for peptides from intermediate filaments.
