Lactose-conjugated polyion complex micelles incorporating plasmid DNA as a targetable gene vector system: their preparation and gene transfecting efficiency against cultured HepG2 cells.

alpha-Lactosyl-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) block copolymer (lactose-PEG-PAMA) was synthesized to construct a PIC micellar-type gene vector potentially useful for selective transfection of hepatic cells. Lactose-PEG-PAMA spontaneously formed a polyion complex (PIC) micelle with plasmid DNA (pDNA) encoding luciferase (pGL3-Luc) in aqueous solution without any precipitate formation. The lactosylated PIC micelle thus prepared achieved substantially higher transfection efficiency compared to the control PIC micelle without lactose moieties against HepG2 cells possessing asialoglycoprotein (ASGP) receptors recognizing the beta-d-galactose residue. This pronounced transfection efficacy of the lactosylated PIC micelle was inhibited by the addition of excess asialofetuin (ASF), a natural ligand against the ASGP receptor, indicating ASGP receptor-mediated endocytosis to be a major route of the cellular uptake of the lactosylated micelles. Notably, the lactosylated PIC micelle revealed enhanced transfection compared to the control PIC micelle at a lower dose of pDNA, demonstrating the feasibility of using the ligand-conjugated PIC micellar vector for gene delivery to targeted cells.