Investigating the functionalization of liposomes with NFL-TBS. 40-63 peptide as a promising drug delivery system

[Display omitted] •NFL-peptides adopt diverse ultrastructural organization when functionalizing liposomes.•The BIOT-NFL-peptide is the most adsorbed on the liposome surface.•NFL-peptides are enhancing cellular uptake of liposomes in GBM cells.•Liposome functionalization with NFL-peptides is a promising GBM targeting nanosystem. The NFL-peptide was discovered almost 20 years ago, and its targeting properties were assessed alone or in combination with lipid nanocapsules (LNC), magnetic porous silicon nanorods, or gold nanoparticles. Results highlighted a better targeting of cancer cells, in particular glioblastoma and pancreas cancer. Considering the large use of liposomes (LPs) as an hydrophilic drug delivery system, this study explored the possibility to functionalize liposomes with three different sequences of NFL-peptides: native (NFL-peptide), biotinylated (BIOT-NFL) and coupled to fluorescein (FAM-NFL). Dynamic Light Scattering (DLS) complemented by cryo-electron microscopy (CEM) showed a peculiar ultrastructural arrangement between NFL-peptides and liposomes. Based on this architectural interaction, we investigated the biological contribution of these peptides in LPs-DiD glioblastoma cellular uptake. Flow cytometry complemented by confocal microscopy experiments demonstrated a consequent and systematic increased uptake of LPs-DiD into F98 cells when their surface was decorated with NFL-peptides. The intra-cellular distribution of these liposomes via an organelle tracker indicated the presence of LPs-DiD in lysosomes after 4 h. Based on the properties of this NFL-peptide, we showed in this work the crucial role of NFL peptide as an effective and promising actor to potentiate nanoparticles entry in glioblastoma cell lines.