肝星状细胞
纤维化
化学
体内
癌症研究
炎症
分泌物
细胞生物学
免疫学
医学
生物
病理
生物化学
生物技术
作者
Jie‐Hua Xing,Li‐Shuang Hou,Kaichao Zhang,Yaowen Zhang,Chenxi Zheng,Zedong Cai,Bingdong Sui,Siyuan Zhou,Wei He,Bang‐Le Zhang
标识
DOI:10.1016/j.jconrel.2024.09.046
摘要
Liver fibrosis represents an inevitable stage of various chronic liver diseases. The activated hepatic stellate cells (aHSCs) are the main drivers for promoting the development of liver fibrosis. Meanwhile, liver macrophages can secrete pro-inflammatory cytokines, thus accelerating the deterioration of the liver. Regulating both aHSCs and the inflammatory microenvironment in the liver simultaneously may be an effective strategy for treating liver fibrosis. A multi-pronged nano-bioconjugated system, HNP-B-aEV, was developed according to the above strategy. Based on cell aggregate-derived extracellular vesicles (aEVs) and hydroxychloroquine (HCQ)-loaded nanoparticles (HNP) modified with retinol, HNP-B-aEV is prepared via a reactive oxygen species (ROS)-responsive boronate linker. In the ROS-rich microenvironment of liver fibrosis, aEVs and HNP are released, eliminating ROS, and targeting aHSCs and macrophages respectively to inhibit the activation of HSCs. Both in vitro and in vivo studies demonstrated that HNP-B-aEV can significantly inhibit the release of inflammatory factors from M1 macrophages, remodeling the microenvironment and preventing the activation of HSCs, offering a multi-pronged treatment for liver fibrosis. This strategy can inhibit the progression of liver fibrosis at its source, providing a new perspective for the clinical treatment of liver fibrosis.
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