Copper-Based Nanoparticles for Effective Treatment Against Sepsis-Induced Lung Injury in Mice Model

Int J Nanomedicine. 2024 Dec 17:19:13507-13524. doi: 10.2147/IJN.S488357. eCollection 2024.

Abstract

Introduction: Lung injury, a common complication of sepsis, arises from elevated reactive oxygen species (ROS), mitochondrial dysfunction, and cell death driven by inflammation. In this study, a novel class of ultrasmall nanoparticles (Cu4.5O USNPs) was developed to address sepsis-induced lung injury (SILI).

Methods: The synthesized nanoparticles were thoroughly characterized to assess their properties. In vitro experiments were conducted to determine the biologically effective concentration and elucidate the anti-inflammatory mechanism of action. These findings were further supported by in vivo studies, showcasing the material's efficacy in mitigating SILI.

Results: The Cu4.5O USNPs demonstrated remarkable scavenging capabilities for hydrogen peroxide (H2O2), superoxide anions (O2 -), and hydroxyl radicals (·OH), attributed to their catalase (CAT)- and superoxide dismutase (SOD)-like activities. Additionally, the nanoparticles exhibited strong anti-inflammatory effects, preserved mitochondrial homeostasis through potent ROS scavenging, and significantly reduced cell death. In vivo studies on mice further validated their protective role against SILI.

The conclusion: This study highlights the therapeutic potential of Cu4.5O USNPs in treating sepsis-induced lung injury by effectively scavenging ROS and reducing cell death. These findings provide compelling evidence for the future use of copper-based nanoparticles as antioxidant therapeutics.

Keywords: anti-inflammation; lung injury; mitochondria; reactive oxygen species scavenging; ultrasmall copper-based nanoparticles.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Copper* / administration & dosage
  • Copper* / chemistry
  • Copper* / pharmacology
  • Disease Models, Animal*
  • Hydrogen Peroxide
  • Lung Injury* / drug therapy
  • Male
  • Metal Nanoparticles* / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species* / metabolism
  • Sepsis* / complications
  • Sepsis* / drug therapy
  • Superoxide Dismutase / metabolism

Substances

  • Copper
  • Reactive Oxygen Species
  • Antioxidants
  • Anti-Inflammatory Agents
  • Superoxide Dismutase
  • Hydrogen Peroxide

Grants and funding

This research was funded by the National Natural Science Foundation of China (NSFC, Grant No. 82360023, 81960022, and 81560018), the Natural Science Foundation General Project of Guangxi Province (Grant No. 2020GXNSFAA159123).