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This study develops an oral pH\u2010responsive probiotic\u2010liposome hybrid system (EcN<jats:sup>PIN<\/jats:sup>\u2010L) by conjugating <jats:italic>Escherichia coli<\/jats:italic> Nissle 1917 (EcN) with pinocembrin (PIN)\u2010loaded liposomes (B\u2010Lip\u2010PIN) via biotin\u2010streptavidin binding and encapsulating them in Eudragit L100\u201055 (L100\u201055). The system resists gastric acid, releases bacteria in intestinal pH conditions, and combines PIN's anti\u2010inflammatory properties with EcN's probiotic effects. In irradiated mice, EcN<jats:sup>PIN<\/jats:sup>\u2010L demonstrates effective intestinal colonization and multiple therapeutic benefits: it reduces pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u201017A), enhances intestinal barrier function, and decreases epithelial apoptosis. 16S rRNA sequencing reveals improved microbiota homeostasis with increased beneficial bacteria and decreased harmful species. 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These results highlight EcN<jats:sup>PIN<\/jats:sup>\u2010L as a promising dual\u2010mechanism therapy for radiation\u2010induced intestinal injury, offering targeted delivery and combined anti\u2010inflammatory\/microbiome\u2010modulating action.<\/jats:p>","DOI":"10.1002\/adhm.202501642","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T10:59:57Z","timestamp":1749725997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["pH\u2010Responsive Probiotic\u2010Liposome Hybrid System Synergistically Treats Radiation\u2010Induced Injury via Dual Mechanisms of Anti\u2010Inflammatory and Microbiome Modulation"],"prefix":"10.1002","volume":"14","author":[{"given":"Heshuo","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Pathology at the First Affiliated Hospital State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection &amp; 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