Membrane Fluidity as a New Means 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 nontumor cells have been reported, they are not systematically 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, we achieved selective targeting on four cancer cell lines of varying aggressiveness. Furthermore, using membrane-embedded and inner core-encapsulated fluorophores, we assessed the mechanism of this interaction 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.