肝靶向脂质体-姜源外泌体混合纳米载体协同减轻肥胖诱导的非酒精性脂肪性肝炎。

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yuhong Ma, Yukun Ma, Zhen Yuan, Jingxian Han, Dechun Huang, Hongliang Qian
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引用次数: 0

摘要

持续高热量饮食会导致内脏脂肪组织中脂质的过度积累,从而增加非酒精性脂肪性肝炎(NASH)的风险。本文研究了姜源性外泌体(G-Exos),该外泌体装载小檗碱(G-Exos@B),通过熊脱氧胆酸(UDCA)引入的脂质体(RAL)的聚结形成GR-Exos@B,促进靶向递送到肝脏,从而有效干预NASH。G-Exos的引入使GR-Exos@B能够有效地克服多肠屏障,促进它们以完整的形式从细胞中排出。有趣的是,RAL的肝脏靶向性使GR-Exos比G-Exos更有效地渗透肝脏,导致肝脏积累量增加2.39倍。体内实验显示,与GR-Exos相比,小檗碱和GR-Exos的双重ROS消耗协同增强了抗氧化应激和肝细胞脂肪变性的治疗效果。此外,G-Exos的巨噬细胞靶向能力被用来抑制肝脏NLRP3炎性体复合物的激活,从M1促炎状态转变为M2抗炎状态,这有助于降低肝巨噬细胞水平,随后减少脂质积累。同时,GR-Exos@B主要通过增强AMPK/AKT/IRS-1信号通路和抑制GSK3-β功能来改善胰岛素敏感性。因此,GR-Exos@B有望成为减轻肥胖诱导的NASH治疗的潜在策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hepatic-Targeted Liposomes-Ginger-Derived Exosomes Hybrid Nanocarrier for Synergistic Alleviation of Obesity-Induced Nonalcoholic Steatohepatitis.

Continued consumption of a high-calorie diet results in the excessive accumulation of lipids in visceral adipose tissue, thereby increasing the risk of nonalcoholic steatohepatitis (NASH). Herein, ginger-derived exosomes (G-Exos) loaded with berberine (G-Exos@B) to facilitate targeted delivery to the liver through the formation of GR-Exos@B via the coalescence of ursodeoxycholic acid (UDCA)-introduced liposomes (RAL) for effective NASH intervention are developed. The introduction of G-Exos significantly equipped GR-Exos@B to effectively overcome the multi-intestinal barrier, facilitating their exit from the cell in an intact form. Interestingly, the hepatic-targeting of RAL allowed GR-Exos to penetrate the liver more effectively than G-Exos, resulting in 2.39-fold greater accumulation in the liver. In vivo experiments revealed that dual ROS depletion by berberine and GR-Exos synergistically enhanced the therapeutic effect against inhibited oxidative stress and hepatocellular steatosis compared to GR-Exos. Additionally, the macrophage-targeting capability of G-Exos is leveraged to suppress the activation of hepatic NLRP3 inflammasome complexes, transitioning from an M1 pro-inflammatory to an M2 anti-inflammatory state, which helped diminish hepatic macrophage levels and subsequently reduce lipid accumulation. Meanwhile, GR-Exos@B improved insulin sensitivity primarily by strengthening the AMPK/AKT/IRS-1 signaling pathway and inhibiting GSK3-β function. Hence, GR-Exos@B shows promise as a potential strategy for alleviating obesity-induced NASH therapy.

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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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