Integrated natural enzyme and nanozyme nanoreactor for managing cerebral ischemia-reperfusion injury by regulating neuroimmune microenvironment

Colloids Surf B Biointerfaces. 2025 Nov:255:114923. doi: 10.1016/j.colsurfb.2025.114923. Epub 2025 Jul 1.

Abstract

Oxidative stress, predominantly from neuronal mitochondrial damage and the resultant cytokine storm, is central to cerebral ischemia-reperfusion injury (CIRI). Regulation of inflammation and immune microenvironment exerts a vital role in inhibiting the oxidative damage of CIRI. However, the drugs' ability to traverse the blood-brain barrier and their immunoregulatory capacity are limited, impeding the therapeutic effect of CIRI. This study introduces an innovative superoxide dismutase (SOD) equipped ruthenium (Ru) nanozyme (SOD@Ru ZIF nanoreactor) for regulating neuroimmune microenvironment and protecting against CIRI. The nanoreactor can be enriched to the brain lesion site, protecting against oxidative stress-induced damage and nerve cell death, alleviating neuroinflammation by regulating the immune microenvironment, thereby minimizing damage associated with CIRI biological models. Overall, this work introduces a new avenue to significantly reduce CIRI through immune microenvironment regulation.

Keywords: Cerebral ischemia-reperfusion injury; Immune microenvironment; Nanozyme; Neuroinflammation; Oxidative stress.

MeSH terms

  • Animals
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / pathology
  • Male
  • Mice
  • Nanoparticles* / chemistry
  • Oxidative Stress / drug effects
  • Particle Size
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / immunology
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / pathology
  • Ruthenium* / chemistry
  • Superoxide Dismutase* / chemistry
  • Superoxide Dismutase* / metabolism

Substances

  • Superoxide Dismutase
  • Ruthenium