https://scholars.lib.ntu.edu.tw/handle/123456789/628170
標題: | Delivery of nitric oxide with a pH-responsive nanocarrier for the treatment of renal fibrosis | 作者: | Lee, Tsung-Ying Lu, Hung-Hsun HUI-TENG CHENG Huang, Hsi-Chien Tsai, Yun-Jen Chang, I-Hsiang Tu, Chao-Peng Chung, Chieh-Wei Lu, Tsai-Te CHI-HOW PENG Chen, Yunching |
關鍵字: | Fibroblast; Nanocarrier; Nitric oxide; Renal fibrosis | 公開日期: | 18-一月-2023 | 卷: | 354 | 來源出版物: | Journal of controlled release : official journal of the Controlled Release Society | 摘要: | Fibrosis is an excessive accumulation of extracellular matrix (ECM) that may cause severe organ dysfunction. Nitric oxide (NO), a multifunctional gaseous signaling molecule, may inhibit fibrosis, and delivery of NO may serve as a potential antifibrotic strategy. However, major limitations in the application of NO to treat fibrotic diseases include its nonspecificity, short half-life and low availability in fibrotic tissue. Herein, we aimed to develop a stimuli-responsive drug carrier to deliver NO to halt kidney fibrosis. We manufactured a nanoparticle (NP) composed of pH-sensitive poly[2-(diisopropylamino)ethyl methacrylate (PDPA) polymers to encapsulate a NO donor, a dinitrosyl iron complex (DNIC; [Fe2(μ-SEt)2(NO)4]). The NPs were stable at physiological pH 7.4 but disintegrated at pH 4.0-6.0. The NPs showed significant cytotoxicity to cultured human myofibroblasts and were able to inhibit the activation of myofibroblasts, as indicated by a lower expression level of α-smooth muscle actin and the synthesis of a major ECM component, collagen I, in cultured human myofibroblasts. When given to mice treated with unilateral ureteral ligation/obstruction (UUO) to induce kidney fibrosis, these NPs remained in blood at a stable concentration for as long as 24 h and might enter the fibrotic kidneys to suppress myofibroblast activation and collagen I production, leading to a 70% reduction in the fibrotic area. In summary, our strategy to assemble a NO donor, the iron nitrosyl complex DNIC, into pH-responsive NPs proves effective in treating renal fibrosis and warrants further investigation for its therapeutic potential. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/628170 | ISSN: | 01683659 | DOI: | 10.1016/j.jconrel.2022.12.059 |
顯示於: | 醫學系 |
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