Comprehensive evaluation of nanodrug CeO2@PDA-curcumin for ischemic stroke induced by ischemia-reperfusion injury: In vitro and in vivo studies.

Ischemic stroke caused by ischemia-reperfusion (I/R) injury remains a major clinical challenge because the secondary pathological cascade involves oxidative stress, inflammation, endothelial dysfunction, neuronal loss, and mitochondrial injury. In this study, we developed a polydopamine-based nanodrug, CeO2@PDA-curcumin, and systematically evaluated its therapeutic potential in vitro and in vivo. Material characterization confirmed successful preparation of the composite nanoplatform, pH-responsive curcumin release, favorable colloidal stability, and potent radical-scavenging activity. In HUVECs exposed to H2O2-induced oxidative stress, CeO2@PDA-curcumin improved cell viability, reduced intracellular reactive oxygen species, regulated Bax/Bcl-2-related apoptotic signaling, and alleviated mitochondrial membrane potential loss. The inclusion of a free-curcumin group in all cell-based experiments further showed that curcumin contributed independently at the cellular level, although its individual radical-scavenging activity was not directly evaluated in the cell-free DPPH and hydroxyl-radical assays. In the MCAO rat model, CeO2@PDA-curcumin improved cerebral blood flow recovery, reduced infarct size and brain edema, alleviated histopathological injury and apoptosis, promoted angiogenesis and neuronal recovery, and improved neurobehavioral outcomes. Additional in vivo immunofluorescence analyses of PGC-1α, NRF1, and TFAM further supported a mitochondria-associated protective effect in the injured brain. Collectively, these results indicate that CeO2@PDA-curcumin is a promising antioxidant and neuroprotective nanotherapeutic candidate for ischemic stroke associated with I/R injury.