| RRC ID |
43924
|
| 著者 |
Yao XL, Yoshioka Y, Ruan GX, Chen YZ, Mizuguchi H, Mukai Y, Okada N, Gao JQ, Nakagawa S.
|
| タイトル |
Optimization and internalization mechanisms of PEGylated adenovirus vector with targeting peptide for cancer gene therapy.
|
| ジャーナル |
Biomacromolecules
|
| Abstract |
We have previously developed a novel adenovirus vector (Adv) that targeted tumor tissues/vasculatures after systemic administration. The surface of this Adv is conjugated with CGKRK tumor homing peptide by the cross-linking reaction of polyethyleneglycol (PEG). In this study, we showed that the condition of PEG modification was important to minimize the gene expression in normal tissues after systemic treatment. When Adv was modified only with PEG-linked CGKRK, its luciferase expression was enhanced even in the liver tissue, as well as the tumor tissue. However, in the reaction with the mixture of non-cross-linking PEG and PEG-linked CGKRK, we found out that the best modification could suppress its gene expression in the liver, without losing that in the tumor. We also studied the internalization mechanisms of CGKRK-conjugated Adv. Results suggested that there is a specific interaction of the CGKRK peptide with a receptor at the cell surface enabling efficient internalization of CGKRK-conjugated Adv. The presence of cell-surface heparan sulfate is important receptor for the cellular binding and uptake of CGKRK-conjugated Adv. Moreover, macropinocytosis-mediated endocytosis is also important in endocytosis of CGKRK-conjugated Adv, aside from clathrin-mediated and caveolae-mediated endocytosis. These results could help evaluate the potentiality of CGKRK-conjugated Adv as a prototype vector with suitable efficacy and safety for systemic cancer gene therapy.
|
| 巻・号 |
13(8)
|
| ページ |
2402-9
|
| 公開日 |
2012-8-13
|
| DOI |
10.1021/bm300665u
|
| PMID |
22746837
|
| MeSH |
Adenoviridae / chemistry
Adenoviridae / genetics*
Amino Acid Sequence
Animals
Cell Line, Tumor
Cross-Linking Reagents / chemistry*
Endocytosis
Female
Genes, Reporter
Genetic Therapy*
Genetic Vectors
Liver / metabolism
Luciferases, Firefly / biosynthesis
Luciferases, Firefly / genetics
Lung / metabolism
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Neoplasms / therapy*
Peptide Fragments / chemistry*
Polyethylene Glycols / chemistry*
Spleen / metabolism
Transduction, Genetic
Transgenes
|
| IF |
6.092
|
| 引用数 |
21
|
|
WOS 分野
|
POLYMER SCIENCE
CHEMISTRY, ORGANIC
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
B16/BL6(RCB2638) |
