PdZn/CoSA‐NC Nanozymes with Highly Efficient SOD/CAT Activities for Treatment of Osteoarthritis via Regulating Immune Microenvironment

Author:

Yang Xin1,Tan Manli12,Guo Jianfeng13,Xiang Jianhui1,Yin Feiying1,Deng Jiejia2,Luo Ji3,Xiao Shihui3,Mo Miao1,Wang Hanjie2,Zhao Jinmin13,Zheng Li1ORCID,Cheng Jianwen13,Zhong Jingping1

Affiliation:

1. Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co‐constructed By the Province and Ministry Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning Guangxi 530021 China

2. Life Sciences Institute Guangxi Medical University Nanning Guangxi 530021 China

3. Department of Orthopaedics Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical University Nanning Guangxi 530021 China

Abstract

AbstractInflammatory infiltration of synovial M1 macrophages, high levels of ROS, and NO exacerbate osteoarthritis (OA) progression. The PdZn/CoSA‐NC nanozymes, which are highly ordered PdZn intermetallic nanoparticles loaded with Co single atom N‐doped carbon‐rich in multi‐level pores, in an attempt to serve as SOD and CAT mimicking nanozymes for OA therapy is designed. The PdZn/CoSA‐NC nanozymes' high electron transfer and dual active site sufficient exposure enhances free radical adsorption and lower reaction energies, accelerating SOD‐like, CAT‐like, and GPx‐like catalyzed reactions, outperforming CoSA‐NC and PdZn/NC alone. Furthermore, PdZn/CoSA‐NC nanozymes exhibit favorable biocompatibility, reduce synovial macrophage oxidative stress in OA, alleviate hypoxia, restore mitochondrial function, regulate energy metabolism, increase antioxidant factors, and reduce inflammatory factors, thus effectively mitigating the progression of OA. Mechanistically, PdZn/CoSA‐NC nanozymes downregulate M1‐type phenotypic markers like IL‐1β by regulating purine metabolism. The PdZn/CoSA‐NC nanozymes offer a novel approach to treating oxidative stress‐related inflammatory diseases.

Funder

Natural Science Foundation of Guangxi Province

National Natural Science Foundation of China

Publisher

Wiley

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