Mg2+‐Loaded Black Phosphorus Nanosheet Protects against Cerebral Ischemic Injury through Anti‐Oxidative and Anti‐Inflammatory Effects

Abstract Ischemic stroke is a severe neurological disease, with high morbidity and mortality worldwide. To date, the treatment of ischemic stroke is limited, and its consequent ischemia‐reperfusion injury is an important reason for this result. Excessive reactive oxygen species (ROS) and inflammatory storm followed by ischemia‐reperfusion alter the microenvironment of cerebral ischemic penumbra, leading to the devastating damage to the brain. Herein, we design a black phosphorus nanosheets (BPNSs) loaded with magnesium ions (Mg 2+ ) and polydopamine (PBP@Mg) to tackle the above problems. BPNSs of PBP@Mg effectively scavenge excessive ROS in neurocytes. Mg 2+ plays an anti‐inflammatory role in ischemic penumbra. Furthermore, polydopamine improves the stability of BPNSs. PBP@Mg is subsequently injected into the lateral ventricle of a rat model of ischemic stroke, resulting in an improvement of the ischemic microenvironment and a reduction in ischemic volume. BPNSs of PBP@Mg counteract against the excessive generation of ROS and the neuronal apoptosis in ischemic penumbra. Meanwhile, PBP@Mg dramatically suppresses inflammation by promoting the transformation of microglia from M1 to M2 in ischemic penumbra. PBP@Mg group exhibit a significantly better performance in neurofunctional behavior compared to ischemic group. Taken together, this study provides a novel therapeutic approach for cerebral ischemia‐reperfusion injury via anti‐oxidative and anti‐inflammatory effects.