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Coordinated therapy that restores barrier integrity and interrupts pathogenic gut\u2010liver crosstalk remains a significant challenge. To address this, a colon\u2010targeted delivery system based on sodium alginate microspheres is developed for loading copper\u2010kaempferol nanocomplexes (CuK@SA). Upon oral administration, this system prolongs the retention and release of CuK NCs in the colon. Through scavenging reactive oxygen and nitrogen species (ROS\/RNS), regulating macrophage polarization, improving microbial homeostasis, and enhancing tight junction protein expression, it multi\u2010dimensionally restores intestinal barrier integrity and effectively blocks the translocation of endotoxins to the liver via the gut\u2010liver axis. In mouse models of dextran sulfate sodium (DSS)\u2010induced colitis and high\u2010fat\u2010diet\u2010induced MASH, CuK@SA significantly alleviates intestinal inflammation, repairs barrier structure, and simultaneously improves hepatic steatosis and inflammatory responses. This work provides a novel strategy for synchronously targeting IBD and its systemic complications through modulation of the gut\u2010liver axis.<\/jats:p>","DOI":"10.1002\/adhm.71668","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:08:28Z","timestamp":1788239308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal Barrier Repair\u2010Based Copper\u2010Kaempferol Nanocomplexes Regulates Gut\u2010Liver Axis Homeostasis"],"prefix":"10.1002","volume":"15","author":[{"given":"Weiqi","family":"Li","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Anhui Medical University  Hefei P. R. 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