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

作　　者：Xuzhuo Chen Yi Du Yazi Huang Xianhao Zhou Xinru Xie Chang Li Chen Zhao Fengrong Dai Xijiao Yu Shanyong Zhang 

机构地区：[1]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 [2]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 [3]State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences,Fuzhou 350002,China [4]Department of Chemistry,College of Chemistry and Environment,Guangdong Ocean University,Zhanjiang 524088,China [5]Department of Orthopedics,Shanghai Key Laboratory of Orthopedic Implant,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China

出　　处：《Nano Research》2024年第6期5374-5389,共16页纳米研究（英文版）

基　　金：the Open Project of Shandong Provincial Health Commission Key Laboratory of Oral Diseases and Tissue Regeneration(No.2023KF001);China Postdoctoral Science Foundation(No.2023M732281);the National Natural Science Foundation of China(Nos.82301108,and 82071135);the Natural Science Foundation of Shandong Province(No.ZR2021MH230).

摘　　要：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 Cu_(11),which possesses remarkable enzyme-like and ROS-scavenging activities.This unique combination of properties qualifies Cu_(11)as an attractive anti-inflammatory and anti-ROS agent.The Cu_(11)clusterzymes specifically target mitochondria,effectively scavenging excessive reactive oxygen species(ROS)and reducing oxidative stress.Furthermore,Cu_(11)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 Cu_(11)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 Cu_(11)make it a promising candidate for further development and clinical translation.

关 键 词：NANOCLUSTERS clusterzymes oxidative stress TENDINOPATHY reactive oxygen species(ROS) 

分 类 号：R87[医药卫生—运动医学]