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负载吡非尼酮的介孔聚多巴胺靶向成纤维细胞活化蛋白用于肺纤维化治疗

Mesoporous Polydopamine Loaded Pirfenidone Target to Fibroblast Activation Protein for Pulmonary Fibrosis Therapy.

作者信息

Fang Qi, Liu Shaoyu, Cui Jiangyu, Zhao Ruiyue, Han Qian, Hou Peng, Li Youcai, Lv Jie, Zhang Xiaoyao, Luo Qun, Wang Xinlu

机构信息

Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

出版信息

Front Bioeng Biotechnol. 2022 Jul 22;10:920766. doi: 10.3389/fbioe.2022.920766. eCollection 2022.

Abstract

Recently, fibroblast activation protein (FAP), an overexpressed transmembrane protein of activated fibroblast in pulmonary fibrosis, has been considered as the new target for diagnosing and treating pulmonary fibrosis. In this work, mesoporous polydopamine (MPDA), which is facile prepared and easily modified, is developed as a carrier to load antifibrosis drug pirfenidone (PFD) and linking FAP inhibitor (FAPI) to realize lesion-targeted drug delivery for pulmonary fibrosis therapy. We have found that PFD@MPDA-FAPI is well biocompatible and with good properties of antifibrosis, when ICG labels MPDA-FAPI, the accumulation of the nanodrug at the fibrosis lung can be observed by NIR imaging, and the antifibrosis properties of PFD@MPDA-FAPI were also better than those of pure PFD and PFD@MPDA; therefore, the easily produced and biocompatible nanodrug PFD@MPDA-FAPI developed in this study is promising for further clinical translations in pulmonary fibrosis antifibrosis therapy.

摘要

最近,成纤维细胞活化蛋白(FAP),一种在肺纤维化中活化成纤维细胞过度表达的跨膜蛋白,已被视为诊断和治疗肺纤维化的新靶点。在这项工作中,易于制备且易于修饰的介孔聚多巴胺(MPDA)被开发为载体,用于负载抗纤维化药物吡非尼酮(PFD)并连接FAP抑制剂(FAPI),以实现针对肺纤维化治疗的病灶靶向给药。我们发现PFD@MPDA-FAPI具有良好的生物相容性和抗纤维化特性,当吲哚菁绿(ICG)标记MPDA-FAPI时,通过近红外成像可以观察到纳米药物在纤维化肺中的蓄积,并且PFD@MPDA-FAPI的抗纤维化特性也优于纯PFD和PFD@MPDA;因此,本研究中开发的易于制备且具有生物相容性的纳米药物PFD@MPDA-FAPI在肺纤维化抗纤维化治疗中具有进一步临床转化的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1437/9363109/17394edf1274/FBIOE_fbioe-2022-920766_wc_sch1.jpg

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