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While reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and a coordinated cell death pathway PANoptosis have been implicated, their interplay as a unified pathogenic axis remains elusive. Here, by integrating multi\u2010omics analyses of clinical databases and patient samples, we systematically identified and validated the ROS\/NETs\/PANoptosis axis as a central driver of hepatocyte damage across multiple ALI etiologies. To therapeutically target this axis, we engineered a liver\u2010targeted gallium\u2010quercetin nanocomposite (Ga@Que) via coordination\u2010driven self\u2010assembly. Ga@Que effectively overcomes the poor bioavailability of natural quercetin. In murine models of acetaminophen\u2010induced and ischemia\u2010reperfusion liver injury, Ga@Que exhibited significant liver accumulation, potently scavenged ROS, suppressed neutrophil infiltration and NETs formation, and attenuated PANoptosis. Consequently, Ga@Que treatment markedly mitigated liver damage and inflammation, outperforming its individual components. Our study not only delineates a novel pathogenic paradigm in ALI but also introduces Ga@Que as a promising precision nanotherapeutic, offering a synergistic and translatable strategy to disrupt this deleterious cascade.<\/jats:p>","DOI":"10.1002\/advs.202524135","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:38:58Z","timestamp":1774528738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liver\u2010Targeted Gallium\u2010Polyphenol Network by Disrupting the ROS\/NETs\/PANoptosis Axis for Precision Acute Liver Injury Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaopeng","family":"Cai","sequence":"first","affiliation":[{"name":"Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang 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