RRC ID 6195
Author Vachutinsky Y, Oba M, Miyata K, Hiki S, Kano MR, Nishiyama N, Koyama H, Miyazono K, Kataoka K.
Title Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles.
Journal 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.
Volume 149(1)
Pages 51-7
Published 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
Times Cited 64
DNA material pCAcc-Luc+ (RDB02443)