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

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 (Mg²⁺) and polydopamine (PBP@Mg) to tackle the above problems. BPNSs of PBP@Mg effectively scavenge excessive ROS in neurocytes. Mg²⁺ 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.