Jan, 2011
Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles
JOURNAL OF CONTROLLED RELEASE
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- Volume
- 149
- Number
- 1
- First page
- 51
- Last page
- 57
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.jconrel.2010.02.002
- Publisher
- ELSEVIER SCIENCE BV
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.
- Link information
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- DOI
- https://doi.org/10.1016/j.jconrel.2010.02.002
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/20138936
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000286850700009&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-78651244521&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0003-1593-1855
- ID information
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- DOI : 10.1016/j.jconrel.2010.02.002
- ISSN : 0168-3659
- ORCID - Put Code : 38046639
- Pubmed ID : 20138936
- SCOPUS ID : 78651244521
- Web of Science ID : WOS:000286850700009