Synergistic microglial modulation by laminarin-based platinum nanozymes for potential intracerebral hemorrhage

Xiumei Guo1, Qionghua Zheng2, Wen Gao3

  • 1Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China; Laboratory of Clinical Pharmacy, Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China; Medical Center for Neurological Disorders, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, China; Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.

Biomaterials
|March 3, 2025
PubMed

Insights

This study introduces a novel platinum nanozyme (Pt@LA) that reduces brain inflammation and oxidative stress after intracerebral hemorrhage (ICH). Pt@LA effectively regulates microglial polarization, offering a promising new therapeutic strategy for ICH recovery.

Area of Science:

  • Neuroscience
  • Biomaterials Science
  • Nanotechnology

Background:

  • Abnormal microglial activation drives inflammation and brain damage in intracerebral hemorrhage (ICH).
  • Effective ICH treatments require regulating oxidative stress and inhibiting pro-inflammatory M1-like microglia.
  • Antioxidant nanozymes show potential for modulating microglial states, but their role in ICH is underexplored.

Purpose of the Study:

  • To develop and evaluate an ultra-small laminarin-modified platinum nanozyme (Pt@LA) for synergistic regulation of microglial polarization in ICH.
  • To investigate Pt@LA's capacity to alleviate oxidative stress and neuroinflammation post-ICH.
  • To establish a novel therapeutic strategy for ICH leveraging nanozyme technology.

Main Methods:

  • Development of ultra-small (3-4 nm) laminarin-modified platinum nanozymes (Pt@LA).
  • In vitro assessment of Pt@LA's antioxidant (SOD and CAT-like) and anti-inflammatory effects on microglia, including inhibition of Dectin-1/Syk/NF-κB and ROS-mediated NF-κB pathways.
  • In vivo evaluation of Pt@LA in ICH rat models, assessing neuronal protection, glial scar formation, and neurological function.

Main Results:

  • Pt@LA demonstrated effective scavenging of reactive oxygen species (ROS) via superoxide dismutase (SOD) and catalase (CAT)-like activities.
  • In vitro studies showed Pt@LA reduced pro-inflammatory microglia and cytokine expression by inhibiting key inflammatory pathways.
  • In ICH rats, Pt@LA treatment protected neurons, reduced glial scar formation, and improved neurological outcomes.

Conclusions:

  • Pt@LA acts as a potent antioxidant and anti-inflammatory agent by modulating microglial polarization through Dectin-1/Syk/NF-κB and ROS-mediated NF-κB pathways.
  • The developed nanozyme offers a promising therapeutic approach for mitigating oxidative stress and neuroinflammation in ICH.
  • This study bridges nanozyme research and neuroscience, presenting a novel strategy for ICH treatment.

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