Platinum‐Loaded Cerium Oxide Capable of Repairing Neuronal Homeostasis for Cerebral Ischemia‐Reperfusion Injury Therapy

Effective neuroprotective agents are required to prevent neurological damage caused by reactive oxygen species (ROS) generated by cerebral ischemia‐reperfusion injury (CIRI) following an acute ischemic stroke. Herein, it is aimed to develop the neuroprotective agents of cerium oxide loaded with platinum clusters engineered modifications (Ptn‐CeO2). The density functional theory calculations show that Ptn‐CeO2 could effectively scavenge ROS, including hydroxyl radicals (·OH) and superoxide anions (·O2−). In addition, Ptn‐CeO2 exhibits the superoxide dismutase‐ and catalase‐like enzyme activities, which is capable of scavenging hydrogen peroxide (H2O2). The in vitro studies show that Ptn‐CeO2 could adjust the restoration of the mitochondrial metabolism to ROS homeostasis, rebalance cytokines, and feature high biocompatibility. The studies in mice CIRI demonstrate that Ptn‐CeO2 could also restore cytokine levels, reduce cysteine aspartate‐specific protease (cleaved Caspase 3) levels, and induce the polarization of microglia to M2‐type macrophages, thus inhibiting the inflammatory responses. As a result, Ptn‐CeO2 inhibits the reperfusion‐induced neuronal apoptosis, relieves the infarct volume, reduces the neurological severity score, and improves cognitive function. Overall, these findings suggest that the prominent neuroprotective effect of the engineered Ptn‐CeO2 has a significant neuroprotective effect and provides a potential therapeutic alternative for CIRI. This study reports a cerium oxide loaded with platinum clusters (Ptn‐CeO2) nano‐heterostructure for the treatment of cerebral ischemia‐reperfusion injury. In addition to efficiently scavenging reactive oxygen species, Ptn‐CeO2 remodels the in vivo immune‐inflammatory microenvironments and prevents neuronal apoptosis, and ultimately improves neurobehavioral manifestations. This strategy offers a potential option for clinical applications.