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Here a novel strategy to fabricate nanotherapeutic formulations employing genetically engineered IL1ra protein complexes, yielding ultralong\u2010lasting bioefficacy is developed rationally. Using rat models, it is shown that these nanotherapeutics significantly improved drug regimen to a single subcutaneous administration in a 14\u2010day therapy, suggesting their extraordinary bioavailability and ultralong\u2010acting pharmacokinetics. Specifically, the half\u2010life and bioavailability of the nanoformulations are boosted to the level of 30 h and by 7 times, respectively, significantly greater than other systems. This new strategy thus holds great promise to potently improve patient compliance in RA therapy, and it can be adapted for other therapies that suffer similar drawbacks.<\/jats:p>","DOI":"10.1002\/adma.202100098","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T01:59:01Z","timestamp":1616032741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations"],"prefix":"10.1002","volume":"33","author":[{"given":"Chao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Chemistry Tsinghua University  Beijing 100084 China"},{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"School of Engineering and Applied Sciences Harvard University  29 Oxford Street 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