Glycerol-Based Polymer to Improve the Cellular Uptake of Liposomes

Nanomedicines modify the pharmacology of pharmaceutical ingredients, but most require cell internalization to deliver their payloads. Hence, modifying the surface properties of nanomedicines can improve their interactions with cells and modulate their pharmacology. Herein, we devised a polymer that increases how nanomedicines are internalized by cells. The alkylated poly(monoglycerol acrylate) (PMGA) polymer was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization with a terminal double 18-carbon moiety that allows its anchoring on the surface of liposomes. PMGA-decorated liposomes are internalized more efficiently in immune cells, compared to formulations without the polymer. Using inhibitors of internalization pathways, we established that PMGA promotes cell entry by the fast endophilin-mediated endocytosis (FEME). In comparison, noncoated control liposomes were mostly internalized by clathrin-mediated endocytosis. This work highlights the potential of PMGA to increase the internalization of nanomedicines by immune cells, and target a novel internalization pathway.