| RRC ID |
18995
|
| 著者 |
Chang KL, Higuchi Y, Kawakami S, Yamashita F, Hashida M.
|
| タイトル |
Efficient gene transfection by histidine-modified chitosan through enhancement of endosomal escape.
|
| ジャーナル |
Bioconjug Chem
|
| Abstract |
Chitosan has the potential to be a biocompatible gene carrier. However, the transfection efficiency of chitosan is low because of the slow endosomal escape rate. The buffering capacity of histidine in the endosomal pH range would help the escape of plasmid DNA (pDNA) from endosomes. In this study, histidine was introduced into chitosan to improve the transfection efficiency. Chitosan and histidine were linked by disulfide bonds provided by 2-iminothiolane and cysteine. The complexes were prepared by mixing chitosan or histidine-modified chitosan with plasmid DNA. A broader buffering range of histidine-modified chitosan was observed, and the cellular uptake of histidine-modified chitosan/pDNA complexes was higher than that of chitosan/pDNA complexes. Although chitosan/tetramethylrhodamine (TMR)-pDNA complexes were trapped in the vesicles in cytosol, TMR-pDNA carried by histidine-modified chitosan was more widely distributed in the cytosol. This result suggests that histidine can help pDNA escape from endosomes with the help of the high buffering capacity. The gene expression of histidine-modified chitosan/pDNA complexes was higher than that of chitosan/pDNA complexes. These results suggest that histidine modification improves the transfection efficiency of chitosan.
|
| 巻・号 |
21(6)
|
| ページ |
1087-95
|
| 公開日 |
2010-6-16
|
| DOI |
10.1021/bc1000609
|
| PMID |
20499901
|
| MeSH |
Chitosan / chemistry
Chitosan / metabolism*
Chitosan / pharmacology*
Cysteine / chemistry
Cysteine / metabolism
Cytosol / drug effects
Cytosol / metabolism
DNA / chemistry
DNA / metabolism
Disulfides / chemistry
Disulfides / metabolism
Endosomes / drug effects*
Endosomes / metabolism*
Gene Expression
Histidine / chemistry*
Hydrogen-Ion Concentration
Imidoesters / chemistry
Imidoesters / metabolism
Plasmids / chemistry
Plasmids / genetics
Plasmids / metabolism
Rhodamines / chemistry
Rhodamines / metabolism
Transfection / methods*
|
| IF |
4.031
|
| 引用数 |
101
|
|
WOS 分野
|
CHEMISTRY, ORGANIC
BIOCHEMICAL RESEARCH METHODS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CHEMISTRY, MULTIDISCIPLINARY
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
