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

Daisuke Wakebayashi; Nobuhiro Nishiyama; Yuichi Yamasaki; Keiji Itaka; Naoki Kanayama; Atsushi Harada; Yukio Nagasaki; Kazunori Kataoka

doi:10.1016/j.jconrel.2004.01.003

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

J Control Release. 2004 Mar 24;95(3):653-64. doi: 10.1016/j.jconrel.2004.01.003.

Authors

Daisuke Wakebayashi¹, Nobuhiro Nishiyama, Yuichi Yamasaki, Keiji Itaka, Naoki Kanayama, Atsushi Harada, Yukio Nagasaki, Kazunori Kataoka

Affiliation

¹ Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan.

PMID: 15023474
DOI: 10.1016/j.jconrel.2004.01.003

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
DNA / genetics*
Drug Evaluation, Preclinical / methods
Gene Transfer Techniques*
Genetic Vectors / genetics
Humans
Lactose / chemistry*
Liver Neoplasms / pathology
Micelles*
Plasmids / genetics*
Polyethylene Glycols / chemistry*
Transfection / methods

Substances

Micelles
Polyethylene Glycols
DNA
Lactose