RRC ID 42584
Author Hashimoto M, Morimoto M, Saimoto H, Shigemasa Y, Sato T.
Title Lactosylated chitosan for DNA delivery into hepatocytes: the effect of lactosylation on the physicochemical properties and intracellular trafficking of pDNA/chitosan complexes.
Journal Bioconjug Chem
Abstract Chitosan is a useful nonviral vector for gene delivery. To make a pDNA/chitosan complex specific to hepatocytes, lactose-modified chitosan (lac-chitosan) was synthesized. When the percentage of lactose residues substituted was 8%, lac-chitosan showed excellent DNA-binding ability, good protection of DNA from nuclease, and the suppression of self-aggregation and serum-induced aggregation. Although the cellular uptake efficiency of the pDNA/lac-chitosan complex was almost the same as that of the pDNA/chitosan complex, the cell transfection efficiency of the former was greater for HepG2 cells having asialoglycoprotein receptors. Inhibitor of endocytosis such as bafilomycin A1 and nocodazole significantly reduced the transfection efficiency of the pDNA/lac-chitosan complex. Observations with a confocal laser scanning microscope indicated that the pDNA/lac-chitosan complexes traversed endocytic compartments more rapidly than the pDNA/chitosan complex. Furthermore, the pDNA/lac-chitosan complexes were delivered to the late endosome and have the advantage of delivering DNA to the perinuclear region.
Volume 17(2)
Pages 309-16
Published 2006-1-1
DOI 10.1021/bc050228h
PMID 16536460
MeSH Animals Biocompatible Materials* / chemistry Biocompatible Materials* / metabolism Biological Transport Carbohydrate Conformation Carbohydrate Sequence Cell Line Chitosan* / chemistry Chitosan* / metabolism DNA / metabolism* Deoxyribonuclease I / metabolism Hepatocytes / metabolism* Humans Lactose / chemistry* Lactose / metabolism Macromolecular Substances Molecular Sequence Data Molecular Structure Transfection
IF 4.031
Times Cited 104
WOS Category CHEMISTRY, ORGANIC BIOCHEMICAL RESEARCH METHODS CHEMISTRY, MULTIDISCIPLINARY BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells COS-7(RCB0539) Hep G2