Antiangiogenic Gene Therapy of Solid Tumor by Systemic Injection of Polyplex Micelles Loading Plasmid DNA Encoding Soluble Flt-1

被引：60

作者：

Oba, Makoto ^{[2
]}

Vachutinsky, Yelena ^{[3
]}

Miyata, Kanjiro ^{[4
]}

Kano, Mitsunobu R. ^{[5
,6
]}

Ikeda, Sorato

Nishiyama, Nobuhiro ^{[4
]}

Itaka, Keiji ^{[4
]}

Miyazono, Kohei ^{[5
,6
]}

Koyama, Hiroyuki ^{[2
]}

Kataoka, Kazunori ^{[1
,3
,4
,5
]}

机构：

[1] Univ Tokyo, Dept Mat Engn, Grad Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Clin Vasc Regenerat, Bunkyo Ku, Tokyo 1138655, Japan

[3] Univ Tokyo, Grad Sch Engn, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan

[4] Univ Tokyo, Ctr Dis Biol & Integrat Med, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan

[5] Univ Tokyo, Ctr NanoBio Integrat, Bunkyo Ku, Tokyo 1138656, Japan

[6] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, Tokyo 1138655, Japan

来源：

MOLECULAR PHARMACEUTICS | 2010年 / 7卷 / 02期

基金：

日本科学技术振兴机构;

关键词：

Polymeric micelle; block copolymer; antiangiogenic tumor gene therapy; sFlt-1; GROWTH-FACTOR RECEPTOR; ANTITUMOR-ACTIVITY; BLOCK-COPOLYMER; CANCER; DELIVERY; EXPRESSION; BEVACIZUMAB; INHIBITION; TRANSFECTION; ANGIOGENESIS;

D O I：

10.1021/mp9002317

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：501 / 509

页数：9

共 31 条

[11] Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR [J].