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However, its constant exposure to harmful substances, such as alcohol, drugs, and toxins, makes it prone to injury. Persistent exposure drives liver disease progression, which causes about \u223c4% of all deaths annually. Current treatments for liver injury, which combine targeted and supportive care, remain limited by poor drug delivery and efficacy. Anti\u2010inflammatory and antioxidant treatments are essential, yet the pathology is a complex interplay of oxidative stress, inflammation, hepatocyte death, and fibrosis, resisting simple interventions. Polyphenols are multi\u2010target compounds, but their efficacy is hindered by conventional drawbacks. Nanotechnology mimics nanoscale biology to improve pharmacokinetics, enable liver\u2010targeted delivery, and support combination therapies. Notably, polyphenols can act as building units for novel nanodrugs or modify other nanoparticles due to structural features. Thus, polyphenol\u2010based nanodrugs achieve efficient liver enrichment and hold unique potential to tackle multiple therapeutic challenges. Herein, this article analyzes the core pathophysiology of liver injury, elaborates on the biological activities of polyphenols and clinical challenges, and focuses on how to leverage the distinctive chemical properties of polyphenols to construct advanced nanodrugs, and how these nanodrugs can address multiple pathogenic facets of liver injury.<\/jats:p>","DOI":"10.1002\/adhm.71320","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:26:40Z","timestamp":1780979200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutually Reinforcing Polyphenol and Nanomedicines: Unlocking the Potential of Polyphenol\u2010Based Nanodrugs for Liver Injury Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Min","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy Xiangya Hospital Central South University  Changsha Hunan P. R. China"},{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan P. R. China"},{"name":"Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences Central South University  Changsha P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan P. R. China"},{"name":"Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences Central South University  Changsha P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruishi","family":"Li","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan P. R. China"},{"name":"Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences Central South University  Changsha P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan P. R. China"},{"name":"Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences Central South University  Changsha P. R. 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