纳米载体
间充质干细胞
小干扰RNA
癌症研究
肌成纤维细胞
癌基因
材料科学
肺纤维化
药物输送
纤维化
核糖核酸
细胞
生物
细胞生物学
医学
病理
纳米技术
细胞周期
生物化学
基因
作者
Qijian Ji,Jiwei Hou,Xueqing Yong,Guangming Gong,Mohd. Muddassir,Tianyu Tang,Jinbing Xie,Wenpei Fan,Xiaoyuan Chen
标识
DOI:10.1002/adma.202007798
摘要
Abstract Inhibiting the myofibroblast differentiation of lung‐resident mesenchymal stem cells (LR‐MSCs) is a promising yet challenging approach for pulmonary fibrosis (PF) therapy. Here, micelles formed by a graft copolymer of multiple PEGs modified branched polyethylenimine are used for delivering runt‐related transcription factor‐1 (RUNX1) small interfering RNA (siRNA) (siRUNX1) to the lung, aiming to inhibit the myofibroblast differentiation of LR‐MSCs. LR‐MSC targeting is achieved by functionalizing the micelle surface with an anti‐stem‐cell antigen‐1 antibody fragment (Fab′). Consequently, therapeutic benefits are obtained by successful suppression of myofibroblast differentiation of LR‐MSCs in bleomycin‐induced PF model mice treated with siRUNX1‐loaded micelles. Furthermore, an excellent synergistic effect of PF therapy is achieved for this micelle system loaded siRUNX1 and glioma‐associated oncogene homolog‐1 (Gli1) small interfering RNA (siGli1), a traditional anti‐PF siRNA of glioma‐associated oncogene homolog‐1. Hence, this work not only provides RUNX1 as a novel PF therapeutic target, but also as a promising dual siRNA‐loaded nanocarrier system for the therapy of PF.
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