Gene transfer efficacies of serum-resistant amino acids-based cationic lipids: dependence on headgroup, lipoplex stability and cellular uptake.

Serum is a major obstacle to efficient cationic liposome-mediated gene transfection. In this paper, three alkaline amino acids based cationic lipids including lysinylated cholesterol (lipid 1), histidinylated cholesterol (lipid 2) and argininylated cholesterol (lipid 3) were used as non-viral gene vectors. The physicochemical properties such as size, Zeta potential, stability and cellular uptake of the lipoplexes formed from lipids 1-3 as well as the transfection efficacies with or without serum were investigated. The results demonstrated that lipid 1 and lipid 3 showed good properties in lipoplex stability and cellular uptake. Interestingly, lipid 3-based liposome showed serum-enhanced effect on the gene transfection. The transfection efficiency of lipid 1 and lipid 3 was remarkably higher than that of lipid 2. Moreover, they exhibited 10-20-fold more efficaciously than the control, 1,2-dioleoyloxy-3-(trimethylammonio)-propane (DOTAP) liposome in serum-containing media. The data suggested the strong effect of the type of the headgroup on gene transfection. The lysine/arginine derivative cationic lipids could be promising nonviral vectors for gene delivery in vivo.