Polyethylene glycol-grafted poly- l-lysine as polymeric gene carrier

Abstract

A new series of gene carriers, polyethylene glycol (PEG)-grafted poly- l-lysine (PLL, mol. wt.=25 000) with three different PEG-grafted ratios (5, 10 and 25 mole%, which means 5, 10 and 25% of ϵ-amino group of PLL was modified by PEG), was synthesized. These new gene carriers, named comb-shaped PEG- g-PLL copolymer, showed a 5- to 30-fold increase in transfection efficiency compared to PLL alone on a human carcinoma cell line. It is likely that Hep G2 cells were transfected by plasmid DNA/PEG- g-PLL complexes through an endocytosis mechanism due to the fact that chloroquine increased transfection efficiency. Although Lipofectin™, a cationic lipid formulation, showed slightly higher transfection efficiency than PEG- g-PLL in Hep G2 cells, our designed PEG- g-PLL demonstrated lower cytotoxicity, early gene expression and maintenance of gene expression for up to 96 h.