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

研究成果: Article

106 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)309-316
ページ数8
ジャーナルBioconjugate Chemistry
17
発行部数2
DOI
出版物ステータスPublished - 2006 3

Fingerprint

Chitosan
Hepatocytes
DNA
Lactose
Transfection
Agglomeration
Asialoglycoprotein Receptor
Nocodazole
Deoxyribonucleases
Endosomes
Hep G2 Cells
Endocytosis
Lasers
Microscopes
Genes
Scanning

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

これを引用

Lactosylated chitosan for DNA delivery into hepatocytes : The effect of lactosylation on the physicochemical properties and intracellular trafficking of pDNA/chitosan complexes. / Hashimoto, Mayu; Morimoto, Minoru; Saimoto, Hiroyuki; Shigemasa, Yoshihiro; Sato, Toshinori.

:: Bioconjugate Chemistry, 巻 17, 番号 2, 03.2006, p. 309-316.

研究成果: Article

@article{938cba2846ec4f6fbccc4474387a2313,
title = "Lactosylated chitosan for DNA delivery into hepatocytes: The effect of lactosylation on the physicochemical properties and intracellular trafficking of pDNA/chitosan complexes",
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.",
author = "Mayu Hashimoto and Minoru Morimoto and Hiroyuki Saimoto and Yoshihiro Shigemasa and Toshinori Sato",
year = "2006",
month = "3",
doi = "10.1021/bc050228h",
language = "English",
volume = "17",
pages = "309--316",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Lactosylated chitosan for DNA delivery into hepatocytes

T2 - The effect of lactosylation on the physicochemical properties and intracellular trafficking of pDNA/chitosan complexes

AU - Hashimoto, Mayu

AU - Morimoto, Minoru

AU - Saimoto, Hiroyuki

AU - Shigemasa, Yoshihiro

AU - Sato, Toshinori

PY - 2006/3

Y1 - 2006/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33645474488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645474488&partnerID=8YFLogxK

U2 - 10.1021/bc050228h

DO - 10.1021/bc050228h

M3 - Article

C2 - 16536460

AN - SCOPUS:33645474488

VL - 17

SP - 309

EP - 316

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 2

ER -