A Co-Doped Fe₃O₄ Nanozyme Shows Enhanced Reactive Oxygen and Nitrogen Species Scavenging Activity and Ameliorates the Deleterious Effects of Ischemic Stroke

Abstract

Acute ischemic stroke has become the major cause of mortality and disability worldwide. Following ischemic stroke, the reperfusion injury is mainly mediated by the burst of reactive oxygen and nitrogen species (RONS). Therefore, blocking the excessive production or removing RONS holds great promise as a potential therapeutic strategy. Herein, we developed a Co-doped Fe3O4 nanozyme that is capable of scavenging H2O2, O2 •–, •NO, and ONOO– in vitro and in vivo and provides neuroprotection against ischemic stroke. In vitro experiments showed that pre-incubation with the Co-Fe3O4 nanozyme could prevent neurotoxicity and neuroinflammation induced by H2O2 or lipopolysaccharide, respectively, in HT22 cells. After intravenous administration, the Co-Fe3O4 nanozyme showed no signs of toxicity in peripheral organs of C57BL/6J mice, even after prolonged delivery for 4 weeks. In permanent photothrombotic stroke model and transient middle cerebral artery occlusion stroke model, the Co-Fe3O4 nanozyme specifically accumulated in the infarct rim at 72 h post-stroke and was endocytosed by neurons, astrocytes, microglia, and endothelial cells. Importantly, the Co-Fe3O4 nanozyme delivery reduced the infarct volume in both stroke models. The observation that the Co-Fe3O4 nanozyme was efficacious in two well-characterized ischemic stroke models provides strong evidence that it represents a powerful tool for targeting oxidative and nitrosative stress in the ischemic brain.

TiO2 Nanoflowers Decorated with FeOx Nanocluster and Single Atoms by Atomic Layer Deposition for Peroxidase-Mimicking Nanozymes

“…Nanozymes are the nanomaterials with intrinsic enzyme-like properties, and engineering nanomaterials with enzyme-mimicking characteristics has drawn increasing attention. − However, the catalytic efficiency of the most reported nanozymes is still lower than that of natural enzymes, which limits the practical application of nanozymes . The rational design and controllable synthesis are the key to the preparation of highly active nanozymes.…”

Breakthroughs in nanozyme-inspired application diversity

“…Furthermore, Co–Fe 3 O 4 nanozyme was proved to act effectively toward neuroinflammatory reactions, while in short- and long-term investigations of healthy mice, it would not induce inflammatory response or damage in peripheral organs. 117…”

“…Furthermore, Co-Fe 3 O 4 nanozyme was proved to act effectively toward neuroinflammatory reactions, while in short-and long-term investigations of healthy mice, it would not induce inflammatory response or damage in peripheral organs. 117 After cardiovascular illnesses, strokes are the second biggest cause of death worldwide. The most common type of stroke is an ischemic stroke, which is primarily caused by an abrupt stoppage of the blood flow to the brain together with an explosive rise in ROS.…”

Structure design mechanisms and inflammatory disease applications of nanozymes

“…Liu et al developed a Co-doped Fe 3 O 4 nanozyme that is capable of scavenging excess RONS in reperfusion injury to provide neuroprotection against ischemic stroke. 202 The Co-doped Fe 3 O 4 exhibited uptake by neurons, astrocytes, microglia, and endothelial cells, and it was found to be accumulated in the rim of the penumbra, providing neuroprotection 72 h post-stroke in transient middle cerebral artery occlusion (MCAO). Similar results were also confirmed in the photothrombotic stroke model.…”