Membrane Fluidity as a New Mean to Selectively Target Cancer Cells with Fusogenic Lipid Carriers.

Lipid-based carriers such as liposomes represent one of the most advanced classes of drug delivery systems. Their clinical success relies on their composition, similar to that of the cell membrane. Their cellular specificity often relies on a ligand-receptor interaction. Although differences in the physicochemical properties of the cell membrane between tumor and non-tumor cells have been reported, they have little been used for drug delivery purposes. In this report, a new approach was developed to ensure selective targeting based on physical compatibility between the target and the carrier membranes. By modulating the liposome composition and thus, its membrane fluidity, selective targeting was achieved on four cancer cell lines of varying aggressiveness. Furthermore, using membrane-embedded and inner core-encapsulated fluorophores, the mechanism of this interaction was assessed to be based on the fusion of the liposome with the cell membranes. Membrane fluidity is therefore a major parameter to be considered when designing lipid drug carriers, as a promising, lower cost, alternative to current targeting strategies based on covalent grafting.