[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-439689-105":59,"doc-detail-439689-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","constructing-dual-atomic-fe-fe-sites-nanozyme-for-targeted-osteoarthritis-therapy-through-mitigating-oxidative-stress-and-cartilage-degeneration","Constructing Dual-Atomic Fe-Fe Sites Nanozyme for Targeted Osteoarthritis Therapy through Mitigating Oxidative Stress and Cartilage Degeneration","","Osteoarthritis progression is driven by excessive reactive oxygen species (ROS) that injure chondrocytes and articular cartilage. This study proposes dual-site nanozymes by creating Fe-Fe dimers on nitrogen-doped porous carbon (Fe2-NCs) to eliminate ROS via a co-adsorption mechanism targeting the superoxide radical. Density functional theory shows Fe-Fe synergy modulates oxygen adsorption, accelerates O-O bond cleavage, and enhances antioxidant behavior. In vitro and in vivo results indicate ROS mitigation, improved mitochondrial function, reduced apoptosis, lowered COX-2 and MMP-13 activity, and suppression of NF-κB-mediated collagen II breakdown.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/constructing-dual-atomic-fe-fe-sites-nanozyme-for-targeted-osteoarthritis-therapy-through-mitigating-oxidative-stress-and-cartilage-degeneration/439689/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/constructing-dual-atomic-fe-fe-sites-nanozyme-for-targeted-osteoarthritis-therapy-through-mitigating-oxidative-stress-and-cartilage-degeneration/439689.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-01","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role do reactive oxygen species (ROS) play in osteoarthritis progression?","Question",{"text":112,"@type":113},"Excessive ROS damages chondrocytes and articular cartilage and disrupts mitochondrial redox homeostasis, amplifying pro-inflammatory signaling and apoptosis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the Fe2-NCs nanozyme target ROS?",{"text":117,"@type":113},"Fe2-NCs are designed with nitrogen-doped porous carbon hosting Fe-Fe dimers that eliminate excessive ROS through a co-adsorption mechanism involving the superoxide radical.",{"name":119,"@type":110,"acceptedAnswer":120},"What biological effects do Fe2-NCs show in vitro and in vivo?",{"text":121,"@type":113},"Fe2-NCs mitigate ROS, protect chondrocytes from oxidative-stress-induced apoptosis, strengthen mitochondrial function by inhibiting NOX4 and restoring ATP levels, and downregulate inflammatory and cartilage-degrading mediators such as COX-2 and MMP-13.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},439689,1790718770,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nConstructing Dual-Atomic Fe─Fe Sites Nanozyme for Targeted Osteoarthritis Therapy through Mitigating Oxidative Stress and Cartilage Degeneration  \nTing Ying, Qi Wang, Dejian Li, Yao Wang,* Pengfang Zhang, Chengqing Yi,* and Rui Zhu*  \nOsteoarthritis progression is driven by excessive reactive oxygen species (ROS), which causes significant secondary damage to chondrocytes and articular cartilage. Herein, the concept of holding desired dual-site nanozymes is proposed through developing Fe─Fe dimers on nitrogen-doped porous carbon (Fe2-NCs) to eliminate excessive ROS through the co-adsorption mechanism of superoxide radical. The Fe2-NCs present an enhanced ROS performance, effectively mimicking key antioxidant enzymes. Density functional theory calculations indicate that the synergistic effects ofthe Fe─Fe dimer can modulate oxygen adsorption configurations and accelerating O─O bond-cleavage. In vitro and in vivo results show that Fe2-NCs effectively mitigate ROS, protecting chondrocytes from oxidative stress-induced apoptosis. The mitochondrial function can be strengthened over Fe2-NCs by inhibiting NOX4 expression, restoring ATP levels, and normalizing COXIV expression. Additionally, Fe2-NCs significantly downregulate the  \npro-inflammatory mediator COX-2, inhibit MMP-13-mediated cartilage degradation, and slow down the type II collagen (COL2) breakdown through the inhibition of NF-􀀂B signaling pathway.  \nThe excessive accumulation of ROS can directly damage key cellular structures, while disturbing the redox homeostasis within mitochondria, activating critical signaling pathways, thereby amplifying the release of proinflammatory cytokines and exacerbating chondrocyte apoptosis. [6–10] By doing so, this cascade culminates in catastrophic degradation of cartilage extracellular matrix (ECM) components—primarily collagen II and aggrecan—establishing a selfperpetuating ROS-inflammation-ECM destruction cycle. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx) have recently garnered significant attention due to their catalytic reactions within cells to remove ROS, thereby regulating the redox state and protecting cells from oxidative damage. [11,12] However, the low stability of these natural enzymes under pathological conditions limited their practical applications. [13,14] Consequently, thereis a pressing need to enhance the stability  \n1. Introduction  \nOsteoarthritis (OA) is a prevalent degenerative joint disorder.[1] Growing evidence has highlighted the critical involvement of reactive oxygen species (ROS) in the pathophysiology of OA. [2–5] In the OA pathological microevironment, excessive ROS (e.g.,•OH, H2 O2 , O2•− ) act as pivotal drivers of disease progression. [6]  \nof these antioxidant enzymes to unlock their full potential for therapeutic use in regenerative medicine and other clinical applications. Studies highlighted the exceptional catalytic performance of single-atom NCs, which capitalize on the utilization of single metal atoms and the strong interactions between metal centers and supports, conferring a remarkable catalytic activity and selectivity of ROS removal. [15–18] Despite their promising ca-  \nT. Ying, R. Zhu  \nShanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)  \nSchool of Medicine Tongji University Shanghai 200092, China  \nE-mail: [zhurui@tongji.edu.cn](zhurui@tongji.edu.cn)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202508073](https://doi.org/10.1002/advs.202508073)[ ](https://doi.org/10.1002/advs.202508073)© 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.","cbCail2elkzdl4w2","https://ap.wps.com/l/cbCail2elkzdl4w2","pdf",5571128,22,"English","# Introduction\n## Reactive oxygen species in osteoarthritis pathology\n## Antioxidant enzymes and the need for improved stability\n## Nanozyme strategies: single-atom and dual-atom approaches\n# Proposed Fe2-NCs nanozyme concept and mechanism","[{\"question\":\"What role do reactive oxygen species (ROS) play in osteoarthritis progression?\",\"answer\":\"Excessive ROS damages chondrocytes and articular cartilage and disrupts mitochondrial redox homeostasis, amplifying pro-inflammatory signaling and apoptosis.\"},{\"question\":\"How does the Fe2-NCs nanozyme target ROS?\",\"answer\":\"Fe2-NCs are designed with nitrogen-doped porous carbon hosting Fe-Fe dimers that eliminate excessive ROS through a co-adsorption mechanism involving the superoxide radical.\"},{\"question\":\"What biological effects do Fe2-NCs show in vitro and in vivo?\",\"answer\":\"Fe2-NCs mitigate ROS, protect chondrocytes from oxidative-stress-induced apoptosis, strengthen mitochondrial function by inhibiting NOX4 and restoring ATP levels, and downregulate inflammatory and cartilage-degrading mediators such as COX-2 and MMP-13.\"}]","Constructing Dual-Atomic Fe-Fe Sites Nanozyme for Targeted Osteoarthritis Therapy through Mitigating Oxidative Stress and Cartilage Degeneration | PDF",1790689902,55]