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journal article·2026-06Open access

Liver‐Targeted Gallium‐Polyphenol Network by Disrupting the ROS/NETs/PANoptosis Axis for Precision Acute Liver Injury Therapy

Xiaopeng Cai, Jian He, Jingwen Deng, Ziwei Wang, Zhongshu Wu, Kaiyue Wang, Xiang Zheng, Zhenzhen Gao, Xi Ma, Shumei Wei, Xiangrong Hu, Yuan Ding, Weilin Wang, Min Zhou

Advanced Science· Volume 13· Issue 32
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Source abstract

Abstract

ABSTRACT Acute liver injury (ALI), driven by diverse insults such as drug toxicity and ischemia‐reperfusion, poses a high mortality risk and lacks targeted therapies. 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‐omics 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‐targeted gallium‐quercetin nanocomposite (Ga@Que) via coordination‐driven self‐assembly. Ga@Que effectively overcomes the poor bioavailability of natural quercetin. In murine models of acetaminophen‐induced and ischemia‐reperfusion 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.
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Research context

Nanomaterials

OpenAlex topics: Neutrophil, Myeloperoxidase and Oxidative Mechanisms · Drug-Induced Hepatotoxicity and Protection · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China

Zhejiang University‐University of Edinburgh Institute (ZJU‐UoE Institute) and Liangzhu Laboratory Zhejiang University School of Medicine Zhejiang University Haining Zhejiang China

Zhejiang University‐Ordos City Etuoke Banner Joint Research Center Zhejiang University Haining Zhejiang China

Department of Medical Oncology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China

Zhejiang University‐University of Edinburgh Institute (ZJU‐UoE Institute) Zhejiang University Haining China

Department of Radiology Sir Run Run Shaw Hospital of School of Medicine Zhejiang University Hangzhou Zhejiang China

Department of surgery and International Institutes of Medicine The Fourth Affiliated Hospital Zhejiang University School of Medicine Yiwu Zhejiang China

Departments of Clinical Pathology The Second Affiliated Hospital of Medical College of Zhejiang University Hangzhou Zhejiang China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shandong Province

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