TY - JOUR
T1 - Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles
AU - Vachutinsky, Yelena
AU - Oba, Makoto
AU - Miyata, Kanjiro
AU - Hiki, Shigehiro
AU - Kano, Mitsunobu R.
AU - Nishiyama, Nobuhiro
AU - Koyama, Hiroyuki
AU - Miyazono, Kohei
AU - Kataoka, Kazunori
N1 - Funding Information:
This work was financially supported in part by the Core Research Program for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency (JST) as well as by Grants-in-Aid for Young Scientists (A). We express our appreciation to Prof. M. Shibuya (Tokyo Medical and Dental University) for providing pVL 1393 baculovirus vector pDNA encoding human sFlt-1. We thank Ms. S. Ogura (The University of Tokyo) for her technical assistance.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1/5
Y1 - 2011/1/5
N2 - 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.
AB - 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.
KW - Antiangiogenic gene therapy
KW - Cyclic RGD peptide
KW - Poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLys)
KW - Polyplex micelle
KW - sFlt-1
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U2 - 10.1016/j.jconrel.2010.02.002
DO - 10.1016/j.jconrel.2010.02.002
M3 - Article
C2 - 20138936
AN - SCOPUS:78651244521
VL - 149
SP - 51
EP - 57
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -