Novel Cationic Transfection Lipids for Use in Liposomal Gene Delivery

摘要

A novel series of nontoxic and non-glycerol-based simple monocationic transfection lipids containing one or two hydroxyethyl groups directly linked to the positively charged nitrogen atom were synthesized. The in vitro transfection efficiencies of these new liposomal gene delivery reagents were better than that of lipofectamine, a transfection agent widely used in cationic lipid-mediated gene transfer. The most efficient transfection formulation was observed to be a 1:1:0.3 mole ratio of DHDEAB (N,N-di-n-hexadecyl-N,N-dihydroxyethylammonium bromide)/cholesterol/HDEAB (N-n-hexadecyl-N,N-dihydroxyethylammonium bromide) using a DHDEAB-to-DNA charge ratio (+/-) of 0.3/1. Observation of good transfection at charge ratios lower than one suggests that the amphiphile/DNA complex may have a net negative charge. Our results reemphasize the important point that in cationic lipid-mediated gene delivery, the overall charge of the lipid-DNA complex need not always be positive. In addition, our transfection results imply that favorable hydrogen-bonding interactions between the lipid head groups and the cell surface of biological membranes may have some role in improving the transfection efficiency in cationic lipid-mediated gene delivery.