Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue

被引：36

作者：

Miyata, Kanjiro ^{[1
,6
]}

Oba, Makoto ^{[2
]}

Kano, Mitsunobu R. ^{[3
,6
]}

Fukushima, Shigeto ^{[4
]}

Vachutinsky, Yelena ^{[1
]}

Han, Muri ^{[5
]}

Koyama, Hiroyuki ^{[2
]}

Miyazono, Kohei ^{[3
,6
]}

Nishiyama, Nobuhiro ^{[4
,6
]}

Kataoka, Kazunori ^{[1
,4
,5
,6
]}

机构：

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

[2] Univ Tokyo, Dept Clin Vasc Regenerat, Grad Sch Med, Bunkyo Ku, Tokyo 1138656, Japan

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

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

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

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

来源：

PHARMACEUTICAL RESEARCH | 2008年 / 25卷 / 12期

关键词：

gene delivery; PEG; polyplex micelle; TGF-beta inhibitor; triblock copolymer;

D O I：

10.1007/s11095-008-9720-2

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-beta type I receptor (T beta R-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.

引用

页码：2924 / 2936

页数：13

共 27 条

[1] Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation [J].