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aHSCs-targeted bimetallic nanozymes and luteolin-loaded liposomes: Synergistic reversal of liver fibrosis via antioxidant, cellular senescence, and cellular apoptotic mechanisms

肝星状细胞 化学 纤维化 药物输送 细胞外基质 细胞生物学 癌症研究 体内 肝病 基质金属蛋白酶 药理学 细胞凋亡 靶向给药 氧化应激 体外 肝纤维化 纳米载体 活性氧 药品 纳米囊 慢性肝病 微泡 肝损伤 肝细胞学 分泌物 肝癌 基质(化学分析) 细胞 下调和上调 信号转导 药物开发 双金属片
作者
Zihao Sun,Chuipeng Liang,Yuxin Zhao,Jijiao Wu,Lin Wen,Xiaolian Liu,Mingyi Shi,Xiaofang Li
出处
期刊:Materials today bio [Elsevier BV]
卷期号:34: 102201-102201 被引量:1
标识
DOI:10.1016/j.mtbio.2025.102201
摘要

Liver fibrosis is a prevalent pathological process in the development of a range of chronic liver diseases. Hepatic stellate cells (HSCs) are known to be highly activated in the Liver fbrosis environment, and the proliferation of activated HSCs (aHSCs) and the secretion of associated extracellular matrix are crucial in the process of Liver fibrosis, which in turn promotes the development of Liver fibrosis. Concurrently, the inhibition of HSCs activation and the induction of aHSCs senescence/apoptosis have been identified as a therapeutic strategy that exhibits numerous synergistic mechanisms. In addition, the efficacy of clinical treatment is constrained by a number of factors, including the limited selectivity of pharmaceuticals and the inefficiency of drug delivery mechanisms. Consequently, the present study proposes a Luteolin-loaded liposome (LUT@LIP-BSA) and Ce/Mn bimetallic nanozyme (CMB) dual nanodelivery system, which has been modified by BSA to target aHSCs. The results of both in vitro and in vivo experiments demonstrated that the aHSCs-targeted dual delivery system combining LUT@LIP-BSA with CMB exhibited effective targeting delivery capacity to aHSCs. In vitro, LUT@LIP-BSA effectively induced senescence, apoptosis, and counteracted oxidative stress in aHSCs. These effects were confirmed in vivo. Consequently, this combination reduced extracellular matrix production and deposition, thereby inhibiting liver fibrosis. This combinatorial strategy provides a promising foundation for the construction and clinical application of hybrid delivery systems that synergize metal nanoenzymes with natural drugs as an effective targeted therapeutic approach for liver fibrosis.
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