Noncovalenly PEGylated CTGF siRNA/PDMAEMA complex for pulmonary treatment of bleomycin-induced lung fibrosis

被引：39

作者：

Sung, Dong Kyung ^{[1
]}

Kong, Won Ho ^{[2
]}

Park, Kitae ^{[3
]}

Kim, Ji Hyun ^{[4
]}

Kim, Mi Young ^{[4
]}

Kim, Hyemin ^{[2
]}

Hahn, Sei Kwang ^{[2
,3
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul 135710, South Korea

[2] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea

[3] Pohang Univ Sci & Technol POSTECH, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, Kyungbuk, South Korea

[4] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

来源：

BIOMATERIALS | 2013年 / 34卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

Poly(dimethylamino)ethylmethacrylate; CTGF siRNA; Bleomycin; Pulmonary drug delivery; Lung fibrosis; TISSUE GROWTH-FACTOR; DELIVERY; APOPTOSIS; SIRNA; MODEL;

D O I：

10.1016/j.biomaterials.2012.09.061

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

On the basis of wide biomedical applications of methacrylate polymers, we previously developed non-covalently post-PEGylated ternary complex of siRNA using poly(dimethylamino)ethylmethacrylate (PDMAEMA) and its copolymer with poly(alpha-methylether-omega-methacrylate-ethyleneglycol) [PMAPEG]. In this work, we investigated the antifibrotic effect of connective tissue growth factor siRNA (siCTGF)/PDMAEMA/PDMAEMA-b-PMAPEG complex for the treatment of bleomycin-induced pulmonary fibrosis. After orotracheal administration to fibrotic Sprague Dawley (SD) model rats, FAM-labeled siCTGF complex was effectively delivered to the cells in the lung. The siCTGF ternary complex resulted in a significant reduction in target gene expression, collagen deposition, inflammatory cytokines production, and drastic attenuation of pulmonary fibrosis in pathophysiological analysis. Furthermore, the survival rate was remarkably increased to the statistically significant level in comparison with the scrambled siCTGF treatment group. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1261 / 1269

页数：9

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