A Co-Doped Fe3O4 Nanozyme Shows Enhanced Reactive Oxygen and Nitrogen Species Scavenging Activity and Ameliorates the Deleterious Effects of Ischemic Stroke
A Co-Doped Fe3O4 Nanozyme Shows Enhanced Reactive Oxygen and Nitrogen Species Scavenging Activity and Ameliorates the Deleterious Effects of Ischemic Stroke
复制标题
共掺杂 Fe3O4 纳米酶显示出增强的活性氧和氮清除活性并改善缺血性中风的有害影响
DOI：
10.1021/acsami.1c06449
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发表时间：
2021-09-21
影响因子：
9.5
通讯作者：
Wang, Ya-Chao
中科院分区：
文献类型：
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作者：
Liu, Yunsheng;Wang, Xiaojun;Wang, Ya-Chao
急性缺血性脑卒中已成为世界范围内死亡和致残的主要原因。缺血性脑卒中后，再灌注损伤主要由活性氧和氮类（RONS）的爆发介导。因此，阻断RONS的过度产生或去除RONS作为一种潜在的治疗策略具有很大的希望。在此，我们开发了一种Co掺杂的Fe 3 O 4纳米酶，其能够在体外和体内清除H2 O2、O-2（中心点-）、（NO）-N-中心点和ONOO-，并提供对缺血性中风的神经保护。体外实验表明，与Co-Fe_3 O_4纳米酶预孵育可以防止过氧化氢或脂多糖诱导的神经毒性和神经炎症，分别在HT 22细胞。静脉给药后，Co-Fe 3 O 4纳米酶在C57 BL/6 J小鼠的外周器官中没有显示出毒性迹象，即使在延长递送4周后也是如此。在永久性光血栓性中风模型和短暂性大脑中动脉闭塞中风模型中，Co-Fe 3 O 4纳米酶在中风后72 h特异性地积聚在梗死边缘，并被神经元、星形胶质细胞、小胶质细胞和内皮细胞内吞。重要的是，Co-Fe 3 O 4纳米酶递送减少了两种中风模型中的梗死体积。Co-Fe 3 O 4纳米酶在两种充分表征的缺血性中风模型中有效的观察结果提供了强有力的证据，表明它是靶向缺血性脑中氧化和亚硝化应激的有力工具。
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.