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 (center dot OH) and superoxide anions (center dot 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. image