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构建非化学计量氧化铜上的富电子钌簇以高效清除生物催化活性氧来治疗炎症性脊髓损伤。

Constructing Electron-Rich Ru Clusters on Non-Stoichiometric Copper Hydroxide for Superior Biocatalytic ROS Scavenging to Treat Inflammatory Spinal Cord Injury.

机构信息

Engineering Research Center of Oral Translational Medicine, Ministry of Education, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.

出版信息

Adv Mater. 2024 Nov;36(48):e2411618. doi: 10.1002/adma.202411618. Epub 2024 Oct 12.

DOI:10.1002/adma.202411618
PMID:39394880
Abstract

Traumatic spinal cord injury (SCI) represents a complex neuropathological challenge that significantly impacts the well-being of affected individuals. The quest for efficacious antioxidant and anti-inflammatory therapies is both a compelling necessity and a formidable challenge. Here, in this work, the innovative synthesis of electron-rich Ru clusters on non-stoichiometric copper hydroxide that contain oxygen vacancy defects (Ru/def-Cu(OH)), which can function as a biocatalytic reactive oxygen species (ROS) scavenger for efficiently suppressing the inflammatory cascade reactions and modulating the endogenous microenvironments in SCI, is introduced. The studies reveal that the unique oxygen vacancies promote electron redistribution and amplify electron accumulation at Ru clusters, thus enhancing the catalytic activity of Ru/def-Cu(OH) in multielectron reactions involving oxygen-containing intermediates. These advancements endow the Ru/def-Cu(OH) with the capacity to mitigate ROS-mediated neuronal death and to foster a reparative microenvironment by dampening inflammatory macrophage responses, meanwhile concurrently stimulating the activity of neural stem cells, anti-inflammatory macrophages, and oligodendrocytes. Consequently, this results in a robust reparative effect on traumatic SCI. It is posited that the synthesized Ru/def-Cu(OH) exhibits unprecedented biocatalytic properties, offering a promising strategy to develop ROS-scavenging and anti-inflammatory materials for the management of traumatic SCI and a spectrum of other diseases associated with oxidative stress.

摘要

创伤性脊髓损伤 (SCI) 是一种复杂的神经病理学挑战,对受影响个体的健康福祉产生重大影响。寻求有效的抗氧化和抗炎治疗既是当务之急,也是一项艰巨的挑战。在这项工作中,我们创新性地合成了富电子 Ru 簇负载在含有氧空位缺陷的非化学计量铜氢氧化物(Ru/def-Cu(OH))上,Ru/def-Cu(OH) 可以作为生物催化活性氧物质 (ROS) 清除剂,有效抑制炎症级联反应,并调节 SCI 中的内源性微环境。研究表明,独特的氧空位促进了电子重新分布并增强了 Ru 簇上的电子积累,从而提高了 Ru/def-Cu(OH) 在涉及含氧中间体的多电子反应中的催化活性。这些进展使 Ru/def-Cu(OH) 具有减轻 ROS 介导的神经元死亡和通过抑制炎症性巨噬细胞反应来促进修复性微环境的能力,同时还能刺激神经干细胞、抗炎性巨噬细胞和少突胶质细胞的活性。因此,这对创伤性 SCI 产生了强大的修复作用。我们假设,合成的 Ru/def-Cu(OH) 表现出前所未有的生物催化特性,为开发用于创伤性 SCI 及其他与氧化应激相关疾病的 ROS 清除和抗炎材料提供了有前景的策略。

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