Dietary Fe₃O₄ Nanozymes Prevent the Injury of Neurons and Blood–Brain Barrier Integrity from Cerebral Ischemic Stroke

Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood–brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (Fe₃O₄) nanoparticles with intrinsic enzyme-like activities. We find that Fe₃O₄ nanozymes exhibit triple enzyme-like activities, peroxidase, catalase, and superoxide dismutase, thus potentially possessing the ability to regulate the ROS level. Importantly, intragastric administration of PEG-modified Fe₃O₄ nanozymes significantly reduces cerebral infarction and neuronal death in a rodent model following cerebral ischemic stroke. Ex vivo analysis shows that PEG-modified Fe₃O₄ nanozymes localize in the cerebral vasculature, ameliorate local redox state with decreased malondialdehyde and increased Cu/Zn SOD, and facilitate blood–brain-barrier recovery by elevating ZO-1 and Claudin-5 in the hippocampus. Altogether, our results suggest that dietary PEG-modified Fe₃O₄ nanozymes can facilitate blood–brain-barrier reconstruction and protect neurons following ischemic stroke.