Dietary Fe₃O₄Nanozymes Prevent the Injury of Neurons and Blood–Brain Barrier Integrity from Cerebral Ischemic Stroke

Abstract

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.

Nanomaterials alleviating redox stress in neurological diseases: mechanisms and applications

“…The main iron oxide nanozyme is Fe 3 O 4 NPs, which have been demonstrated to possess POD-, CAT-, and SOD-mimicking activity [ 9 , 33 ]. The triple-enzyme-like activities of Fe 3 O 4 NPs are attributed to the valence conversion between Fe 3+ and Fe 2+ .…”

“…The triple-enzyme-like activities of Fe 3 O 4 NPs are attributed to the valence conversion between Fe 3+ and Fe 2+ . Fe 3 O 4 NPs can ameliorate the symptoms of neural dysfunction, and they exhibit neuroprotective effects in experimental cerebral ischemic stroke and aged AD models [ 9 , 34 ]. In a cerebral ischemic stroke model that involved Fe 3 O 4 NPs, the infarct size was significantly reduced and more neurons survived in the hippocampus compared to the controls [ 9 ].…”

“…Fe 3 O 4 NPs can ameliorate the symptoms of neural dysfunction, and they exhibit neuroprotective effects in experimental cerebral ischemic stroke and aged AD models [ 9 , 34 ]. In a cerebral ischemic stroke model that involved Fe 3 O 4 NPs, the infarct size was significantly reduced and more neurons survived in the hippocampus compared to the controls [ 9 ]. In aged Drosophila brains, the ROS levels were reduced and the climbing ability was increased after Fe 3 O 4 NP treatment, leading to a prolonged life span in the Drosophila [ 34 ].…”

“…In aged Drosophila brains, the ROS levels were reduced and the climbing ability was increased after Fe 3 O 4 NP treatment, leading to a prolonged life span in the Drosophila [ 34 ]. In addition, researchers have hypothesized that the enzymatic activities of Fe 3 O 4 NPs may indirectly protect cerebral vascular tissues by regulating the level of ROS [ 9 ]. Fe 2 O 3 NPs are another type of iron oxide nanozyme; however, there has been little research on the application of Fe 2 O 3 NPs for neurological disorders, which may be due to their enzyme-like activities being lower than those of Fe 3 O 4 NPs [ 35 ].…”

“…Nanomaterials (NMs) have been discovered to have unique physicochemical properties and an excellent ability to modulate redox stress over the last decade, and are expected to overcome the shortcomings of present medicinal medications. Several NMs have been screened for use in neurological diseases after enormous efforts, such as iron oxide nanoparticles (NPs), cerium oxide NPs (CeO 2 ) NPs, and fullerenes [ 7 – 9 ]. These NMs exhibit considerable biocompatibility, which ensures they can be safely applied in vivo.…”