Lactosylated chitosan for DNA delivery into hepatocytes: The effect of lactosylation on the physicochemical properties and intracellular trafficking of pDNA/chitosan complexes

Mayu Hashimoto, Minoru Morimoto, Hiroyuki Saimoto, Yoshihiro Shigemasa, Toshinori Sato

Research output: Contribution to journalArticle

106 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalBioconjugate Chemistry
Volume17
Issue number2
DOIs
Publication statusPublished - 2006 Mar 1

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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