An Artificial Peroxynitrite‐Resistant Superoxide Dismutase for Acute Kidney Injury Alleviation

IF 13 2区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Small Pub Date : 2025-06-27 DOI:10.1002/smll.202503033
Fengxian Zhang, Ping Gao, Min Qi, Junjie Hu, Xiuxun Wu, Cao Li, Zechao Zhuang, Zhenpeng Qiu, Ziqiang Xu
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引用次数: 0

Abstract

Manganese superoxide dismutase (Mn‐SOD) is the most common natural antioxidant enzyme that defends cells against oxidative stress. However, it is intrinsically vulnerable to nitration by peroxynitrite (ONOO) to result in accumulation of reactive oxygen species and inducement of acute kidney injury (AKI). Designing Mn‐SOD mimics that are both active and resistant to ONOO is essential for advancing artificial enzymes and broadening the application of enzymatic catalytic therapies. Herein, an artificial manganese‐based single‐atom nanozymes (Mn‐O5/CN SAzyme) featuring square‐pyramidal Mn‐O5 active sites and abundant hydroxyl groups is presented. Mn‐O5/CN SAzyme demonstrates excellent biocompatibility, superior SOD‐like activity, and tolerance to ONOO, positioning it as a promising artificial enzyme mimics for alleviating AKI. Theoretical calculations suggest that the square‐pyramidal Mn‐O5 coordination in Mn‐O5/CN SAzyme enhances its SOD‐like activity and ONOO resistance. Mn‐O5/CN SAzyme has high antioxidant efficacy toward HK‐2 cells. It significantly reduces renal oxidative stress and inflammation in AKI mice, without any side effects. Mechanistically, Mn‐O5/CN SAzyme alleviates AKI by suppressing the pro‐inflammatory cytokine cascade driven by the NOD‐like receptor protein 3 (NLRP3)/caspase‐1/gasdermin D pathway. This study highlights the crucial role of the Mn‐O5 coordination structure in enhancing SOD‐like activity and ONOO resistance, presenting a novel strategy for treating inflammatory diseases.
缓解急性肾损伤的人工抗过氧亚硝酸盐超氧化物歧化酶
锰超氧化物歧化酶(Mn‐SOD)是最常见的天然抗氧化酶,可保护细胞免受氧化应激。然而,它本质上容易受到过氧亚硝酸盐(ONOO−)的硝化作用,导致活性氧积累,诱发急性肾损伤(AKI)。设计对ONOO−具有活性和抗性的Mn‐SOD模拟物对于推进人工酶和扩大酶催化疗法的应用至关重要。本文提出了一种人工锰基单原子纳米酶(Mn - O5/CN SAzyme),其具有方形锥体Mn - O5活性位点和丰富的羟基。Mn‐O5/CN SAzyme表现出优异的生物相容性,优异的SOD样活性和对ONOO -的耐受性,使其成为一种有前景的缓解AKI的人工酶模拟物。理论计算表明,Mn - O5/CN SAzyme中的方锥体Mn - O5配位增强了其SOD样活性和ONOO -抗性。Mn‐O5/CN SAzyme对HK‐2细胞具有较高的抗氧化作用。显著降低AKI小鼠肾脏氧化应激和炎症,无任何副作用。机制上,Mn‐O5/CN SAzyme通过抑制NOD样受体蛋白3 (NLRP3)/caspase‐1/gasdermin D通路驱动的促炎细胞因子级联反应来减轻AKI。这项研究强调了Mn - O5配位结构在增强SOD样活性和ONOO -抗性中的关键作用,提出了治疗炎症性疾病的新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Small
Small 工程技术-材料科学:综合
CiteScore
17.70
自引率
3.80%
发文量
1830
审稿时长
2.1 months
期刊介绍: Small serves as an exceptional platform for both experimental and theoretical studies in fundamental and applied interdisciplinary research at the nano- and microscale. The journal offers a compelling mix of peer-reviewed Research Articles, Reviews, Perspectives, and Comments. With a remarkable 2022 Journal Impact Factor of 13.3 (Journal Citation Reports from Clarivate Analytics, 2023), Small remains among the top multidisciplinary journals, covering a wide range of topics at the interface of materials science, chemistry, physics, engineering, medicine, and biology. Small's readership includes biochemists, biologists, biomedical scientists, chemists, engineers, information technologists, materials scientists, physicists, and theoreticians alike.
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