In vitro study of a siRNA delivery liposome constructed with an ionizable cationic lipid.

OBJECTIVES: Small interfering RNA (siRNA) can silence disease-related genes through sequence-specific RNA interference (RNAi). Cationic lipid-based liposomes effectively deliver nucleic acids into the cytoplasm but often exhibit significant toxicity. This study aims to synthesize a novel ionizable lipid, Nε-laruoyl-lysine amide (LKA), from natural amino acids, constructed LKA-based liposomes, and perform physicochemical characterization and cell-based experiments to systematically evaluate the potential of these ionizable lipid-based liposomes for nucleic acid delivery. METHODS: gene silencing was assessed by real-time fluorescence quantitative PCR, and cell viability was determined using cell counting kit-8 (CCK-8). RESULTS: <0.01). CONCLUSIONS: LKA, an ionizable cationic lipid, can form LKA-LP liposomes for siRNA delivery. The system successfully achieved gene silencing at the cellular level, showing specific cytotoxicity to HeLa cells, providing a solid foundation for developing nucleic acid therapeutics using LKA-LP as a nucleic acid delivery vehicle.