RRC ID 11943
Author Oba M, Vachutinsky Y, Miyata K, Kano MR, Ikeda S, Nishiyama N, Itaka K, Miyazono K, Koyama H, Kataoka K.
Title Antiangiogenic gene therapy of solid tumor by systemic injection of polyplex micelles loading plasmid DNA encoding soluble flt-1.
Journal Mol. Pharm.
Abstract In this study, a polyplex micelle was developed as a potential formulation for antiangiogenic gene therapy of subcutaneous pancreatic tumor model. Poly(ethylene glycol)-poly(l-lysine) block copolymers (PEG-PLys) with thiol groups in the side chain of the PLys segment were synthesized and applied for preparation of disulfide cross-linked polyplex micelles through ion complexation with plasmid DNA (pDNA) encoding the soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), which is a potent antiangiogenic molecule. Antitumor activity and gene expression of polyplex micelles with various cross-linking rates were evaluated in mice bearing subcutaneously xenografted BxPC3 cell line, derived from human pancreatic adenocarcinoma, and polyplex micelles with optimal cross-linking rate achieved effective suppression of tumor growth. Significant gene expression of this micelle was detected selectively in tumor tissue, and its antiangiogenic effect was confirmed by decreased vascular density inside the tumor. Therefore, the disulfide cross-linked polyplex micelle loading sFlt-1 pDNA has a great potential for antiangiogenic therapy against subcutaneous pancreatic tumor model by systemic application.
Volume 7(2)
Pages 501-9
Published 2010-4-5
DOI 10.1021/mp9002317
PMID 20178335
MeSH Animals Cell Line Cell Line, Tumor Genetic Therapy / methods* Humans Mice Mice, Inbred BALB C Mice, Nude Micelles* Neovascularization, Pathologic / therapy Pancreatic Neoplasms / therapy Plasmids / genetics* Vascular Endothelial Growth Factor Receptor-1 / genetics Vascular Endothelial Growth Factor Receptor-1 / physiology* Xenograft Model Antitumor Assays
IF 4.556
Times Cited 41
WOS Category PHARMACOLOGY & PHARMACY MEDICINE, RESEARCH & EXPERIMENTAL
Resource
DNA material pCAcc-Luc+ (RDB02443)