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Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive \u03b5-polylysine nanoparticles at low\u2013molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin \u03b1M\u2013mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.<\/jats:p>","DOI":"10.1126\/sciadv.ado7438","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T13:59:07Z","timestamp":1721829547000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":54,"title":["\u201cTwo-birds-one-stone\u201d oral nanotherapeutic designed to target intestinal integrins and regulate redox homeostasis for UC treatment"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6069-8732","authenticated-orcid":true,"given":"Long","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China."},{"name":"Institute of Biopharmaceutical and Health Engineering, 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