Synergistic anti-inflammatory effect of cascade nanozymes for neural recovery in ischemic stroke

Overproduction of reactive oxygen species (ROS) following ischemic injury triggers an inflammatory response, significantly impeding neurological functional recovery. Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment. In this study, we developed an ischemia-homing nanozyme by combining melatonin (MT)-loaded honeycomb manganese dioxide (MnO 2 ) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra. The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier (BBB)-crossing properties to the biomimetic nanozymes. This nanozyme can not only transforms harmfulsuperoxide anion radicals ( • O 2– ) and hydrogen peroxide (H 2 O 2 ) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals ( • OH), dramatically lowering intracellular ROS levels. More importantly, the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress, inhibiting cell apoptosis, and decreasing inflammation. This study may offer a viable approach for the use of nanozymes in treating ischemic stroke. In this study, we developed M2-type microglia membranes-engineered melatonin-loaded MnO 2 nanoparticles (M2-MnO 2 /MT NPs) to various pathogenic components, including overproduced ROS and inflammatory microglia, providing a targeted therapy for ischemic stroke.