Characterization of Ionizable Lipid Membranes for Designing Bioactive Interface of Inorganic Particles

Abstract Magnetic nanoparticles and their composites are attractive candidates for novel photothermal therapy (PTT) agents in cancer treatment. However, the cellular uptake of these artificial particles remains insufficient because foreign materials are easily excreted from cells. Although lipid membrane coating offers a potential solution to this issue, the specific roles of lipid membrane properties, such as membrane fluidity, polarity, and pH responsive surface charge, remain unclear. Herein, we investigated the physicochemical properties of lipid bilayers containing the ionizable cationic lipid, SM-102, and utilized them to functionalize photothermal magnetic composite particles (MCPs). Liposome characterization revealed that the incorporation of SM-102 slightly decreased the membrane fluidity. Coating the photothermal MCPs with SM-102 bilayers successfully imparted pH responsiveness. Consequently, these lipid-coated MCPs (L-MCPs) exhibited enhanced cellular uptake of particles in HeLa cells at acidic pH. Although both uncoated MCPs and L-MCPs were nontoxic under normal conditions, they exhibited cytotoxicity upon simultaneous exposure to NIR (808 nm) light and a direct current magnetic field (150 mT). Local temperature analyses revealed that L-MCP internalization led to elevated local temperatures in the mitochondria, whereas local heating in the lysosomes was reduced compared to pristine MCPs, indicating that coating with SM-102-containing lipid membranes can alter intracellular particle positioning.