(136d) Cholesterol-Peptide Hybrids to Form Liposome-Like Vesicles for Gene Delivery

In this paper, four amphiphilic cholesterol-peptide conjugates were designed and synthesized, and their properties in gene delivery were evaluated in vitro with an aim of developing more efficient gene delivery carriers. These amphiphilic cholesterol-peptide conjugates are composed of hydrophobic cholesterol and positively charged peptides. They were able to self-assemble into micelles at low concentrations and their critical micelle concentrations in phosphate buffered saline (pH 7.4) are ≤ 85 μg/mL. Amphiphilic cholesterol-peptide conjugates condensed DNA more efficiently than a hydrophilic cationic oligoarginine (R10) peptide with no hydrophobic segment. Their transfection efficiencies were at least two orders of magnitude greater than that of R10 peptide in HEK-293 cells. Moreover, the introduction of histidine residues in cholesterol-peptide conjugates led to higher gene expression efficiency compared with cholesterol-peptides without histidine, and the luciferase expression level was comparable or even higher than that induced by PEI at its optimal N/P ratio. This liposome-like vesicle may be a promising gene delivery carrier for intravenous therapy.