RRC ID |
6195
|
著者 |
Vachutinsky Y, Oba M, Miyata K, Hiki S, Kano MR, Nishiyama N, Koyama H, Miyazono K, Kataoka K.
|
タイトル |
Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles.
|
ジャーナル |
J Control Release
|
Abstract |
Disulfide crosslinked polyplex micelles with RGD peptides were formed through ion complexation of thiolated c(RGDfK)-poly(ethylene glycol)-block-poly(L-lysine) (c(RGDfK)-PEG-P(Lys-SH)) and plasmid DNA encoding sFlt-1 and tested for their therapeutic effect in BxPC3 pancreatic adenocarcinoma tumor bearing mice. These micelles, systemically injected, demonstrated significant inhibition of tumor growth up to day 18, as a result of the antiangiogenic effect that was confirmed by vascular density measurements. Significant therapeutic activity of the 15% crosslinked micelle (c(RGDfK)-PEG-P(Lys-SH15)) was achieved by combined effect of increased tumor accumulation, interaction with endothelial cells and enhanced intracellular uptake through receptor-mediated endocytosis. These results suggest that RGD targeted crosslinked polyplex micelles can be effective plasmid DNA carriers for antiangiogenic gene therapy.
|
巻・号 |
149(1)
|
ページ |
51-7
|
公開日 |
2011-1-5
|
DOI |
10.1016/j.jconrel.2010.02.002
|
PII |
S0168-3659(10)00108-2
|
PMID |
20138936
|
MeSH |
Animals
Cell Line, Tumor
Cross-Linking Reagents / chemistry
DNA / administration & dosage*
DNA / genetics
Female
Gene Transfer Techniques*
Genetic Therapy*
Injections, Intravenous
Lysine / analogs & derivatives*
Lysine / chemical synthesis
Lysine / chemistry
Mice
Mice, Inbred BALB C
Micelles
Microvessels / drug effects
Microvessels / ultrastructure
Neoplasm Transplantation
Neovascularization, Pathologic / genetics
Neovascularization, Pathologic / pathology
Neovascularization, Pathologic / prevention & control*
Oligopeptides / chemistry
Pancreatic Neoplasms / blood supply
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / pathology
Pancreatic Neoplasms / therapy*
Peptides, Cyclic / chemical synthesis
Peptides, Cyclic / chemistry*
Plasmids / administration & dosage
Plasmids / genetics
Polyethylene Glycols / chemical synthesis
Polyethylene Glycols / chemistry*
Polylysine / chemistry
Reverse Transcriptase Polymerase Chain Reaction
Sulfhydryl Compounds / chemistry
Transfection
Vascular Endothelial Growth Factor Receptor-1 / genetics*
|
IF |
7.727
|
引用数 |
64
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
CHEMISTRY, MULTIDISCIPLINARY
|
リソース情報 |
遺伝子材料 |
pCAcc-Luc+ (RDB02443) |