| RRC ID |
12025
|
| Author |
Oba M, Aoyagi K, Miyata K, Matsumoto Y, Itaka K, Nishiyama N, Yamasaki Y, Koyama H, Kataoka K.
|
| Title |
Polyplex micelles with cyclic RGD peptide ligands and disulfide cross-links directing to the enhanced transfection via controlled intracellular trafficking.
|
| Journal |
Mol Pharm
|
| Abstract |
Thiolated c(RGDfK)-poly(ethylene glycol)-block-poly(lysine) (PEG-PLys), a novel block polymer that has a cyclic RGD peptide in the PEG terminus and thiol groups in the PLys side chain, was prepared and applied to the preparation of targetable disulfide cross-linked polyplex micelles through ion complexation with plasmid DNA (pDNA). The obtained polyplex micelles achieved remarkably enhanced transfection efficiency against cultured HeLa cells possessing alpha(v)beta(3) integrin receptors, which are selectively recognized by cyclic RGD peptides, demonstrating the synergistic effect of cyclic RGD peptide ligands on the micelle surface and disulfide cross-links in the core to exert the smooth release of pDNA in the intracellular environment via reductive cleavage. This enhancement was not due to an increase in the uptake amount of polyplex micelles but to a change in their intracellular trafficking route. Detailed confocal laser scanning microscopic observation revealed that polyplex micelles with cyclic RGD peptide ligands were distributed in the perinuclear region in the early stages preferentially through caveolae-mediated endocytosis, which may be a desirable pathway for avoiding the lysosomal degradation of delivered genes. Hence, this approach to introducing ligands and cross-links into the polyplex micelles is promising for the construction of nonviral gene vectors that enhance transfection by controlling intracellular distribution.
|
| Volume |
5(6)
|
| Pages |
1080-92
|
| Published |
2008-1-1
|
| DOI |
10.1021/mp800070s
|
| PMID |
19434856
|
| MeSH |
Cross-Linking Reagents / chemistry
Disulfides / chemistry
HeLa Cells
Humans
Intracellular Space / metabolism*
Ligands
Micelles*
Peptides, Cyclic / chemistry*
Transfection / methods*
|
| IF |
4.321
|
| Times Cited |
112
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
MEDICINE, RESEARCH & EXPERIMENTAL
|
| Resource |
| DNA material |
pCAcc-Luc+ (RDB02443) |
