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Amino Acid‐Based Cationic Lipids With α‐Tocopherol Hydrophobic Tail for Efficient Gene Delivery

In this work, three amino acid‐based cationic lipids L1‐L3 bearing the same α‐tocopherol moiety and biodegradable ester bond linkage, but differing in the polar head‐group, were prepared and applied as non‐viral gene delivery vectors. The physicochemical properties such as size, zeta‐potential, stability, and cellular uptake of the lipoplexes formed from lipids L1‐L3 as well as the transfection efficacy (TE) were investigated. The results showed that the chemical composition of the cationic head‐group clearly affects the physicochemical parameters of the amino acid‐based lipids, especially the TE. Besides their low cytotoxicity, these lipoplexes also showed comparable TE to commercially available lipofectamine 2000. In particular, dipeptide lipid L3 gave excellent TE, which was 1.8 times higher than bPEI 25k in the presence of 10% serum in Hela cells. These results demonstrate the promising use of novel dipeptide lipids for safe and efficient gene delivery.