| RRC ID |
12028
|
| 著者 |
Oba M, Fukushima S, Kanayama N, Aoyagi K, Nishiyama N, Koyama H, Kataoka K.
|
| タイトル |
Cyclic RGD peptide-conjugated polyplex micelles as a targetable gene delivery system directed to cells possessing alphavbeta3 and alphavbeta5 integrins.
|
| ジャーナル |
Bioconjug Chem
|
| Abstract |
A cyclic RGD peptide-conjugated block copolymer, cyclo[RGDfK(CX-)]-poly(ethylene glycol)-polylysine (c(RGDfK)-PEG-PLys), was synthesized from acetal-PEG-PLys under mild acidic conditions and spontaneously associated with plasmid DNA (pDNA) to form a polyplex micelle in aqueous solution. The cyclic RGD peptide recognizes alphavbeta3 and alphavbeta5 integrin receptors, which play a pivotal role in angiogenesis, vascular intima thickening, and the proliferation of malignant tumors. The c(RGDfK)-PEG-PLys/pDNA polyplex micelle showed a remarkably increased transfection efficiency (TE) compared to the PEG-PLys/pDNA polyplex micelle for the cultured HeLa cells possessing alphavbeta3 and alphavbeta5 integrins. On the other hand, in the transfection against the 293T cells possessing no alphavbeta3 and a few alphavbeta5 integrins, the TE of the c(RGDfK)-PEG-PLys/pDNA micelle showed no increase compared to the TE of the PEG-PLys/pDNA micelle. Flow cytometric analysis revealed a higher uptake of the c(RGDfK)-PEG-PLys/pDNA micelle than the PEG-PLys/pDNA micelle against HeLa cells, consistent with the transfection results. Furthermore, a confocal laser scanning microscopic observation revealed that the pDNA in the c(RGDfK)-PEG-PLys micelle preferentially accumulated in the perinuclear region of the HeLa cells within 3 h of incubation. No such fast and directed accumulation of pDNA to the perinuclear region was observed for the micelles without c(RGDfK) ligands. These results indicate that the increase in the TE induced by the introduction of the c(RGDfK) peptide ligand was due to an increase in cellular uptake as well as facilitated intracellular trafficking of micelles toward the perinuclear region via alphavbeta3 and alphavbeta5 integrin receptor-mediated endocytosis, suggesting that the cyclic RGD peptide-conjugated polyplex micelle has promising feasibility as a site-specifically targetable gene delivery system.
|
| 巻・号 |
18(5)
|
| ページ |
1415-23
|
| 公開日 |
2007-1-1
|
| DOI |
10.1021/bc0700133
|
| PMID |
17595054
|
| MeSH |
Biocompatible Materials / chemical synthesis*
DNA / chemistry
DNA / genetics
Flow Cytometry
Gene Transfer Techniques*
HeLa Cells / metabolism*
Humans
Integrin alphaVbeta3 / metabolism*
Integrins / metabolism*
Lysine / analogs & derivatives
Magnetic Resonance Spectroscopy
Micelles
Peptides, Cyclic / chemical synthesis*
Plasmids / chemistry
Plasmids / genetics
Polyethylene Glycols / chemical synthesis*
Receptors, Vitronectin / metabolism*
Transfection / methods*
|
| IF |
4.031
|
| 引用数 |
152
|
|
WOS 分野
|
CHEMISTRY, ORGANIC
BIOCHEMICAL RESEARCH METHODS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CHEMISTRY, MULTIDISCIPLINARY
|
| リソース情報 |
| 遺伝子材料 |
pCAcc-Luc+ (RDB02443) |
