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Research Article

Ultrasmall copper-based clusterzymes ameliorate Achilles tendinopathy by inhibiting acute oxidative stress

Xuzhuo Chen1,§, Yi Du2,§, Yazi Huang4, Xianhao Zhou5, Xinru Xie1, Chang Li3, Chen Zhao5, Fengrong Dai3( ), Xijiao Yu2( ), Shanyong Zhang1( )
Department of Oral Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China
Department of Endodontics, Central Laboratory, Jinan Stomatological Hospital, Jinan Key Laboratory of Oral Tissue Regeneration, Shandong Provincial Health Commission Key Laboratory of Oral Diseases and Tissue Regeneration, Jinan 250001, China
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China
Department of Chemistry, College of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

§ Xuzhuo Chen and Yi Du contributed equally to this work.

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Graphical Abstract

In this study, we designed and synthesized a copper(I)-based cluster (Cu11) with enzyme-like activities and reactive oxygen species (ROS)-scavenging capabilities, positioning it as a promising candidate for anti-inflammatory and anti-ROS therapy.

Abstract

Tendinopathy is a prevalent musculoskeletal disorder, accounting for over 30% of musculoskeletal lesions. However, current therapeutic strategies for tendinopathy are limited and often yield unsatisfactory clinical outcomes. Therefore, there is a critical need to explore novel therapeutic approaches with minimal side effects for tendinopathy and its early lesions. In this study, we successfully designed and synthesized a copper(I)-based nanocluster, named Cu11, which possesses remarkable enzyme-like and ROS-scavenging activities. This unique combination of properties qualifies Cu11 as an attractive anti-inflammatory and anti-ROS agent. The Cu11 clusterzymes specifically target mitochondria, effectively scavenging excessive reactive oxygen species (ROS) and reducing oxidative stress. Furthermore, Cu11 clusterzymes inhibit the activation of key signaling pathways involved in inflammation, namely tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB, leading to a decrease in the release of proinflammatory cytokines. Excitingly, our in vivo experiments using a collagenase-induced acute Achilles tendinopathy model demonstrated that Cu11 clusterzymes effectively alleviate inflammation and oxidative stress, without causing systemic toxicity. This study highlights the potential of copper-based clusterzymes as therapeutic agents for the treatment of Achilles tendinopathy and other inflammatory diseases. The unique enzyme-like and ROS-scavenging activities of Cu11 make it a promising candidate for further development and clinical translation.

Keywords

nanoclustersclusterzymesoxidative stresstendinopathyreactive oxygen species (ROS)

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Nano Research
Volume 17 Issue 6,
June 2024
Pages 5374-5389
DOI: 10.1007/s12274-024-6426-7
Cite this article:
Chen X, Du Y, Huang Y, et al. Ultrasmall copper-based clusterzymes ameliorate Achilles tendinopathy by inhibiting acute oxidative stress. Nano Research, 2024, 17(6): 5374-5389. https://doi.org/10.1007/s12274-024-6426-7
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Received: 26 October 2023
Revised: 17 December 2023
Accepted: 17 December 2023
Published: 19 January 2024
© Tsinghua University Press 2024
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