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Joint inflammatory pain is a primary reason patients seek care, but systemic drug administration often causes severe side effects, while intra\u2010articular injection suffers from rapid clearance and poor tissue penetration. Herein, we develop nanozyme\u2010based Janus nanomotors loaded with metformin (MET) for reactive oxygen species (ROS)\u2010targeted therapy in OA. Leveraging intrinsic superoxide dismutase (SOD) and catalase (CAT) enzymatic activity, these nanomotors harness pathologically elevated ROS within the articular microenvironment as chemical fuel, achieving self\u2010propelled deep penetration into both cartilage and synovial tissue. This mechanism facilitates simultaneous on\u2010the\u2010move ROS scavenging and sustained deep\u2010tissue MET release, which further restores redox homeostasis and protects chondrocytes by regulating the NRF2\/KEAP1 signaling pathway. Furthermore, the nanomotors can suppress nociceptive signaling in the dorsal root ganglia (DRG), thereby alleviating joint pain and improving mobility. This research offers a novel and efficient approach for cartilage protection and arthritis pain management.<\/jats:p>","DOI":"10.1002\/advs.76314","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:56:20Z","timestamp":1783353380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ROS\u2010Targeted Nanomotor Therapy in OA: Cartilage Protection and Pain Relief"],"prefix":"10.1002","volume":"13","author":[{"given":"Meng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7759-7672","authenticated-orcid":false,"given":"Changyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Tongji Hospital Tongji Medical College 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