Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 39, Pages 46213-46224Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c06449
Keywords
Co-doped Fe3O4 nanozyme; ischemic stroke; photothrombotic stroke; transparent brain; RONS; neuroprotection
Funding
- Guangdong Innovation Platform of Translational Research for Cerebrovascular Diseases
- National Natural Science Foundation of China [81873747, 81760227, 81772685, 81902522, 31950410536, 82003303, 82071471]
- Natural Science Foundation of Guangdong Province [2019A1515010311]
- China Postdoctoral Science Foundation [2019M663104]
- Basic research projects of Shenzhen Science and Technology Program [GJHZ20190820115001765]
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The development of a novel nanozyme capable of scavenging reactive oxygen and nitrogen species during ischemic stroke has shown promising neuroprotective effects in both in vitro and in vivo experiments, demonstrating its potential as a powerful tool for targeting oxidative and nitrosative stress in the ischemic brain.
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, O-2(center dot-), (NO)-N-center dot, and ONOO- in vitro and in vivo and provides neuroprotection against ischemic stroke. In vitro experiments showed that preincubation 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.
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