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

Xiaopeng Cai1, Jian He2,3, Jingwen Deng4

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PubMed
Summary
This summary is machine-generated.

Researchers identified the ROS/NETs/PANoptosis axis as a key driver of acute liver injury (ALI). A novel gallium-quercetin nanocomposite (Ga@Que) effectively targeted this axis, reducing liver damage in preclinical models.

Keywords:
PANoptosisacute liver injurygalliumneutrophil extracellular trapspolyphenolreactive oxygen species

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Area of Science:

  • Hepatology
  • Nanomedicine
  • Immunology

Background:

  • Acute liver injury (ALI) presents a high mortality risk with limited targeted treatments.
  • The interplay between reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and PANoptosis in ALI pathogenesis is not fully understood.
  • Existing therapies for ALI lack specificity and efficacy.

Purpose of the Study:

  • To elucidate the ROS/NETs/PANoptosis axis as a unified pathogenic mechanism in diverse ALI etiologies.
  • To develop and evaluate a novel nanotherapeutic agent targeting this axis for ALI treatment.

Main Methods:

  • Multi-omics analyses of clinical databases and patient samples.
  • Development of a liver-targeted gallium-quercetin nanocomposite (Ga@Que).
  • In vivo evaluation of Ga@Que in murine models of acetaminophen-induced and ischemia-reperfusion liver injury.

Main Results:

  • The ROS/NETs/PANoptosis axis was identified as a central driver of hepatocyte damage in ALI.
  • Ga@Que demonstrated significant liver accumulation, ROS scavenging, and suppression of NETs formation and PANoptosis.
  • Ga@Que treatment significantly mitigated liver damage and inflammation, outperforming individual components.

Conclusions:

  • The ROS/NETs/PANoptosis axis represents a novel pathogenic paradigm in acute liver injury.
  • Ga@Que is a promising precision nanotherapeutic for ALI, offering a synergistic and translatable strategy.
  • Targeting this axis provides a potential new therapeutic avenue for managing acute liver injury.