Hepatocyte-targeted gene transfection of galactosylated chitosan-graft low molecular polyethyleneimine/DNA complexes
10.3969/j.issn.1672-7347.2011.05.001
- VernacularTitle:半乳糖化壳聚糖-低分子聚乙烯亚胺/DNA复合物的肝靶向性研究
- Author:
Pingping TAN
;
Man LI
;
Ying WANG
;
Deyun FENG
- Publication Type:Journal Article
- Keywords:
galactosylated chitosan-graft-polyethyleneimine;
liver-targeting;
receptor-mediated gene transfer
- From:
Journal of Central South University(Medical Sciences)
2011;36(5):369-380
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the hepatocyte targeted specific property of galactosylated chitosan-graft-polyethyleneimine (GC-PEI)/DNA complexes in vitro and in vivo.Methods With the plasmid expressing enhanced green fluorescent protein (pEGFP-C1) as the reporter gene,the formation of GC-PEI/DNA complexes was induced to self-assemble in 0.01 mol/L phosphate buffered saline(PBS),150 mmol/L NaCl,or 5% glucose solution (GS).The complexes were characterized by the particle size,Zeta potential,DNA binding and protection capacity,and further tested for cytotoxicity and hepatocyte targeted degradation of DNaseⅠand the serum,which presented as a well-formed sphere or compacted nucleocapsid structure at a diameter of 50-200 nm.The GC-PEI copolymer showed no obvious toxicity in the tested cell lines.Acute toxicity assay revealed that the mice grew well in 2 weeks with GC-PEI dosage from 50 to 300 μg.The assay by flow cytometry and fluorescent microscope showed that the transfection efficiency in hepatocyte lines (L02,QSG7701/core) was higher than that in non-hepatocyte lines (SGC7901,HBE) in vitro.In vivo,the GFP was obviously expressed in the liver tissue and not expressed in other organs 48 h after the transfection.Conclusion GC-PEI copolymer may carry the exogenous gene specifically to hepatocytes in vitro and in vivo,which has very good liver targeted specific property.
