肝星状细胞膜伪装纳米颗粒靶向递送抗纤维化剂到肝星状细胞,增强抗纤维化效果

IF 9.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Zhaoxia Cheng, Fenfen Li, Yunkai Qie, Jingyi Sun, Yazhou Wang, Ying Zhao* and Guangjun Nie*, 
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引用次数: 0

摘要

肝纤维化的特征是主要由活化的肝星状细胞(hsc)产生的细胞外基质蛋白的过度积累。造血干细胞的活化在推动肝纤维化的进程中起着关键作用。实现抗纤维化药物对活化造血干细胞的特异性靶向递送仍然是一个艰巨的挑战。在这里,我们开发了一种名为HSC- plga -BAY的HSC膜伪装纳米系统,用于将抗纤维化剂BAY 11-7082精确递送到活化的HSC中,以治疗肝纤维化。设计的HSC- plga - bay纳米系统对活化的HSC具有选择性靶向作用,其内化由来自HSC膜的同源细胞粘附分子,即整合素和n -钙粘蛋白介导。此外,我们的研究结果表明,在胆管结扎(BDL)诱导的纤维化小鼠模型中,用HSC-PGA-BAY治疗可显著增加活化的hsc的凋亡并改善肝纤维化的进展。总的来说,hsc靶向治疗平台作为肝纤维化治疗的有效策略具有很大的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Hepatic Stellate Cell Membrane-Camouflaged Nanoparticles for Targeted Delivery of an Antifibrotic Agent to Hepatic Stellate Cells with Enhanced Antifibrosis Efficacy

Hepatic Stellate Cell Membrane-Camouflaged Nanoparticles for Targeted Delivery of an Antifibrotic Agent to Hepatic Stellate Cells with Enhanced Antifibrosis Efficacy

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins primarily produced by activated hepatic stellate cells (HSCs). The activation of HSCs plays a pivotal role in driving the progression of liver fibrosis. Achieving specific targeted delivery of antifibrotic agents toward activated HSCs remains a formidable challenge. Here, we developed an HSC membrane-camouflaged nanosystem, named HSC-PLGA-BAY, for the precise delivery of the antifibrosis agent BAY 11-7082 to activated HSCs in the treatment of liver fibrosis. The designed HSC-PLGA-BAY nanosystem exhibited selective targeting toward activated HSCs, with internalization mediated by homologous cell adhesion molecules from the HSC membrane, namely integrins and N-cadherin. Furthermore, our findings demonstrate that treatment with HSC-PGA-BAY significantly increased apoptosis of activated HSCs and ameliorated liver fibrosis progression in a bile duct ligation (BDL)-induced fibrotic mice model. Collectively, the HSCs-targeted therapeutic platform holds promising potential as an effective strategy for liver fibrosis treatment.

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来源期刊
Nano Letters
Nano Letters 工程技术-材料科学:综合
CiteScore
16.80
自引率
2.80%
发文量
1182
审稿时长
1.4 months
期刊介绍: Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.
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