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Current clinically employed viscosupplementation strategies, such as hyaluronic acid, only offer transient lubrication, and under high\u2010shear conditions, it undergoes rapid viscoelasticity deterioration, greatly limiting lubrication property. Here, we reported a multifunctional nanoplatform system (6S\u2010NP), which integrated stimuli\u2010responsive, self\u2010renewable, supramolecular\u2010synergistic, super\u2010lubricating, sustained\u2010retaining, and senescence\u2010reversible features for achieving adaptive treatment in mechanically aggravated age\u2010related joint disorders. Under shear, the host\u2013guest bonds partially dissociated, which released and redistributed hydrated zwitterionic chains to rebuild a highly lubricated layer and minimize friction. When shear was removed, the bonds spontaneously reformed, the nanocrown assembled back, and the lubricating components were retained for the next cycle. This mechanically programmed dissociation\u2013reassembly cycle maintained ultralow friction over repeated loading, achieving a &gt;90% lower coefficient of friction than commercial hyaluronic acid. The reactive oxygen species\u2010cleavable linkers enabled targeted drug release in inflammatory joints, effectively reducing IL\u20106\/IL\u20101\u03b2, protecting extracellular matrix integrity, and reversing chondrocyte senescence. In load\u2010driven knee osteoarthritis and frequency\u2010driven temporomandibular joint osteoarthritis model, 6S\u2010NP preserved cartilage, suppressed inflammation, and improved joint morphology. The adaptable design principles of 6S\u2010NP could also be extended to other mechanically and oxidatively stressed degenerative conditions, providing a broadly applicable therapeutic strategy.<\/jats:p>","DOI":"10.1002\/adma.75311","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:46:30Z","timestamp":1791535590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Six in One: 6S\u2010NP Supramolecular Nanoparticles for Super\u2010Lubrication, Inflammation Suppression, and Senescence Reversal in Mechanically Aggravated Joint Disorders"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4373-5811","authenticated-orcid":false,"given":"Yinuo","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tribology in Advanced Equipment Department of Mechanical Engineering Tsinghua University  Beijing 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