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.