非共价聚乙二醇化 CTGF siRNA/PDMAEMA 复合物用于博来霉素诱导的肺纤维化的肺部治疗。

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

机构信息

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul 135-710, Republic of Korea.

出版信息

Biomaterials. 2013 Jan;34(4):1261-9. doi: 10.1016/j.biomaterials.2012.09.061. Epub 2012 Oct 24.

Abstract

On the basis of wide biomedical applications of methacrylate polymers, we previously developed noncovalently post-PEGylated ternary complex of siRNA using poly(dimethylamino)ethylmethacrylate (PDMAEMA) and its copolymer with poly(α-methylether-ω-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.

摘要

基于甲基丙烯酸酯聚合物在广泛的生物医学应用,我们之前使用聚(二甲基氨基)乙基甲基丙烯酸酯(PDMAEMA)及其与聚(α-甲基醚-ω-甲基丙烯酸乙酯-乙二醇)[PMAPEG]的共聚物开发了非共价键接枝聚乙二醇的 siRNA 三元复合物。在这项工作中,我们研究了结缔组织生长因子 siRNA(siCTGF)/PDMAEMA/PDMAEMA-b-PMAPEG 复合物用于治疗博来霉素诱导的肺纤维化的抗纤维化作用。经口气管内给药给纤维化的 Sprague Dawley(SD)模型大鼠后,FAM 标记的 siCTGF 复合物有效地递送到肺部的细胞中。siCTGF 三元复合物导致靶基因表达、胶原蛋白沉积、炎症细胞因子产生的显著减少,并在病理生理分析中大大减弱了肺纤维化。此外,与 scrambled siCTGF 治疗组相比,存活率显著提高到统计学显著水平。

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