Plasma membrane lipid bilayer is druggable: Selective delivery of gemcitabine-squalene nano-medicine to cancer cells.

Up to now the lipid bilayers were rarely considered as targets in cancer therapy despite pronounced differences in lipid composition between plasma membranes of benign and malignant cells. In this study we demonstrate that the lipid bilayer of the plasma membrane is druggable and suitable for facilitating selective delivery of amphiphilic gemcitabine-squalene nanomedicines to cancer cells. Data from radioactive assays, fluorescent membrane probes and molecular dynamics simulations provide evidence of selective accumulation of gemcitabine-squalene in the plasma membranes with disrupted lipid asymmetry and its subsequent preferential uptake by malignant cells. This causes pronounced cytotoxicity on cancer cells in comparison to their benign counterparts originating from the same tissue.