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

α-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) mic...

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Bibliographic Details
Published in:Journal of controlled release 2004-03, Vol.95 (3), p.653-664
Main Authors: Wakebayashi, Daisuke, Nishiyama, Nobuhiro, Yamasaki, Yuichi, Itaka, Keiji, Kanayama, Naoki, Harada, Atsushi, Nagasaki, Yukio, Kataoka, Kazunori
Format: Article
Language:English
Subjects:
Biological and medical sciences
Block copolymer
Cell Line, Tumor
DNA - genetics
Drug Evaluation, Preclinical - methods
Gene Transfer Techniques
General pharmacology
Genetic Vectors - genetics
Humans
Lactose
Lactose - chemistry
Liver Neoplasms - pathology
Medical sciences
Micelles
Non-viral gene vector
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Plasmid DNA
Plasmids - genetics
Polyethylene Glycols - chemistry
Polyion complex micelle
Transfection - methods
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Summary:α-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 β- 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.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2004.01.003