Bioactive Nanoenzyme Reverses Oxidative Damage and Endoplasmic Reticulum Stress in Neurons under Ischemic Stroke

Designing translational antioxidative agents that could scavenge free radicals produced during reperfusion in brain ischemia stroke and alleviate neurologic damage is the main objective for ischemic stroke treatment. Herein, we explored and simply synthesized a biomimic and translational Mn₃O₄ nanoenzyme (HSA-Mn₃O₄) to constrain ischemic stroke reperfusion-induced nervous system injury. This nanosystem exhibits reduced levels of inflammation and prolonged circulation time and potent ROS scavenging activities. As expected, HSA-Mn₃O₄ effectively inhibits oxygen and glucose deprivation-mediated cell apoptosis and endoplasmic reticulum stress and demonstrates neuroprotective capacity against ischemic stroke and reperfusion injury of brain tissue. Furthermore, HSA-Mn₃O₄ effectively releases Mn ions and promotes the increase of superoxide dismutase 2 activity. Therefore, HSA-Mn₃O₄ inhibits brain tissue damage by restraining cell apoptosis and endoplasmic reticulum stress in vivo. Taken together, this study not only sheds light on design of biomimic and translational nanomedicine but also reveals the neuroprotective action mechanisms against ischemic stroke and reperfusion injury.