In vitro gene delivery to HepG2 cells using galactosylated 6-amino-6-deoxychitosan as a DNA carrier

Taku Satoh, Shinji Kakimoto, Hiroshi Kano, Mika Nakatani, Seiji Shinkai, Takeshi Nagasaki

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

A chitosan derivative, 6-amino-6-deoxy chitosan (6ACT), was galactosylated and was investigated as a gene carrier. A series of galactose-modified 6ACT (Gal-6ACT) with degrees of substitution (d.s.) ranging from 3% to 50% per pyranose were prepared by reductive alkylation with lactose. DNA retardation assays showed that the electrostatic interaction between Gal-6ACT and plasmid DNA was not changed by galactose modification up to 50% per pyranose of 6ACT. Gal-6ACT with a d.s. of 38% was bound to galactose-recognizing lectin, RCA120. A significant increase in transfection efficiency for HepG2 cells was observed at degree of substitutions ranging from 18% to 50% and at N/P values ranging from 1.5 to 2.5. Under optimum conditions, Gal-6ACT showed about 10 times higher efficiency than 6ACT. However, a slight uptake by the galactose receptors on hepatocytes was observed by flow cytometric analysis. Moreover, Gal-6ACT with a d.s. of 38% mediated efficient gene transfer into both A549 and HeLa cells lacking the galactose receptor. These results suggest that the enhancement of transfection efficiency of Gal-6ACT was not due to the increase of receptor-mediated cellular uptake. In addition, the enhanced gene transfer efficiency was not specific to the galactose modification because the efficiency of glucose-modified 6ACT for HepG2 cells was similar as that of Gal-6ACT.

Original languageEnglish
Pages (from-to)1427-1433
Number of pages7
JournalCarbohydrate Research
Volume342
Issue number11
DOIs
Publication statusPublished - Aug 13 2007

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

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