{"title":"Hepatic-Targeted Liposomes-Ginger-Derived Exosomes Hybrid Nanocarrier for Synergistic Alleviation of Obesity-Induced Nonalcoholic Steatohepatitis.","authors":"Yuhong Ma, Yukun Ma, Zhen Yuan, Jingxian Han, Dechun Huang, Hongliang Qian","doi":"10.1002/adhm.202503076","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03076"},"PeriodicalIF":9.6000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Healthcare Materials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1002/adhm.202503076","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.