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In this study, we developed oxygen\u2010propelled, glutathione (GSH)\u2010responsive stomatocyte nanomotors (MTX\/MnO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010GSH\u2010stomatocytes) for osteoarthritis (OA) treatment. First, polymersomes were assembled composed of block copolymers containing a GSH\u2010cleavable disulfide linker, which were loaded with the therapeutic agent methotrexate (MTX) into their hydrophilic domain. Upon dialysis\u2010induced shape change bowl shaped stomatocytes were formed with manganese dioxide (MnO\n                    <jats:sub>2<\/jats:sub>\n                    ) particles encapsulated into the nanocavity with high loading efficiency. Within the OA microenvironment, MnO\n                    <jats:sub>2<\/jats:sub>\n                    decomposed the inflammatory hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ), generating an O\n                    <jats:sub>2<\/jats:sub>\n                    gradient that propelled the nanomotors and enabled chemotactic movement for targeted cargo delivery. Meanwhile, after cellular uptake elevated GSH levels cleaved the disulfide linkers, inducing the collapse of the stomatocyte structure and the rapid release of MTX. The motility and targeted release behavior of the nanomotors were systematically evaluated both in vitro and in vivo. Experimental results demonstrated that these nanomotors effectively alleviated oxidative stress, inflammation, and cartilage degradation, while exhibiting negligible adverse effects. Overall, this study presents a promising GSH\u2010responsive, nanomotor\u2010based strategy for enhanced osteoarthritis therapy.\n                  <\/jats:p>","DOI":"10.1002\/anie.3640627","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:54:17Z","timestamp":1776844457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bio\u2010Propelled Stomatocyte Nanomotors with Glutathione\u2010Responsiveness for Osteoarthritis Treatment"],"prefix":"10.1002","volume":"65","author":[{"given":"Jianhong","family":"Wang","sequence":"first","affiliation":[{"name":"Bio\u2010Organic Chemistry Department of Biomedical Engineering Institute For Complex Molecular Systems (ICMS) Eindhoven University of Technology  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengsi","family":"Zhan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Advanced Fiber Polymer Materials Shanghai Engineering Research Center of Nano\u2010Biomaterials and Regenerative Medicine College of Biological Science and Medical Engineering Donghua University  Shanghai P. 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