Galactosylated chitosan-graft-polyethylenimine as a gene carrier for hepatocyte targeting.
Chitosans have been proposed as alternative, biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan need to be addressed before clinical application. We prepared galactosylated chitosan-graft-polyethylenimine (GC-g-PEI) copolymer by an imine reaction between periodate-oxidized GC and low-molecular-weight PEI. The molecular weight and composition were characterized using gel permeation chromatography column with multi-angle laser scattering and (1)H nuclear magnetic resonance, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. GC-g-PEI showed good DNA-binding ability and superior protection of DNA from nuclease attack and had low cytotoxicity compared to PEI 25K. GC-g-PEI/DNA complexes showed higher transfection efficiency than PEI 25K in both HepG2 and HeLa cell lines. Transfection efficiency into HepG2, which has asialoglycoprotein receptors, was higher than that into HeLa, which does not. GC-g-PEI/DNA complexes also transfected liver cells in vivo after intraperitoneal (i.p.) administration more effectively than PEI 25K. These results suggest that GC-g-PEI can be used in gene therapy to improve transfection efficiency and hepatocyte specificity in vitro and in vivo.
Jiang
H-L
HL
1Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Korea.
Kwon
J-T
JT
Kim
Y-K
YK
Kim
E-M
EM
Arote
R
R
Jeong
H-J
HJ
Nah
J-W
JW
Choi
Y-J
YJ
Akaike
T
T
Cho
M-H
MH
Cho
C-S
CS
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D002460:Cell Line; D048271:Chitosan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage*; D006367:HeLa Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007274:Injections, Intraperitoneal; D008107:Liver Diseases / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D052416:Targeted Gene Repair / Q000379:methods*; D014162:Transfection / Q000379:methods*
D037263:Asialoglycoprotein Receptor; C551320:chitosan-graft-polyethylenimine; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan