期刊
JOURNAL OF CONTROLLED RELEASE
卷 149, 期 1, 页码 51-57出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2010.02.002
关键词
Poly(ethylene glycol)-block-poly(L-lysine) (PEG-PLys); Cyclic RGD peptide; sFlt-1; Antiangiogenic gene therapy; Polyplex micelle
资金
- Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [21659299] Funding Source: KAKEN
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. (C) 2010 Elsevier B.V. All rights reserved.
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