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

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.