Preparation of gene drug delivery systems of cationic peptide lipid with 0G-PAMAM as hydrophilic end and its biological properties evaluation.

Abstract

As an efficient gene delivery, non-viral vectors should have high transfection efficiency, excellent endosomal escape, low cytotoxicity, and the ability to rapidly release the gene into the cytoplasm.Cationic liposome have been widely used as efficient gene carriers, but the cytotoxicity, rapid degradation and low cellular uptake are major drawback impeding its further appolication. Herein, with double lauric acid as hydrophobic chains, tartaric acid as skeleton, 0 generation PAMAM modified with lysine as hydrophilic head, a new type cationic peptide lipid was synthetised. The alkyl chain promote lipid across cell membranes and with membrane fusion, 0 generation PAMAM modified with lysine hydrophilic end amino can contain a large number of protons which can change into ammonium and combine with the DNA negatively charge phosphate groups. It is expected that this carrier has low toxicity, high transfection efficiency and targeting property. By adjusting the cationic liposome/gene weight ratio, the transfection system was optimized to improved gene transfection efficiency, reduce cytotoxicity, and increase property and stability, etc.