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Here, we design and synthesize a pH\/hypoxia dual\u2010responsive pendant azobenzene\u2010functionalized MOF (Azo\u2010MOF). The uniformly distributed azobenzene pendants serve as intrinsic gating sites, forming \u201csnap\u2010top\u201d encapsulation with \u03b2\u2010cyclodextrin through host\u2010guest interactions that prevent premature 6\u2010mercaptopurine leakage while enabling rapid stimuli\u2010triggered release, creating a postmodification\u2010free supramolecular gated delivery nanosystem (CAMM). CAMM exhibits hypoxia\u2010triggered burst release and alkaline\u2010sustained release, with &lt;5.0% drug leakage during gastrointestinal transit and &gt;90.0% cumulative release at inflammatory sites. Notably, the Azo\u2010MOF carrier scavenges reactive oxygen species through synergy between its conjugated\n                    <jats:italic>\u03c0<\/jats:italic>\n                    \u2010system and metal coordination environment, providing antioxidant protection alongside drug delivery. In dextran sulfate sodium\u2010induced colitis models, CAMM outperformed free drug, achieving near\u2010complete weight recovery, downregulating proinflammatory cytokines, restoring intestinal barrier integrity, and rebalancing gut microbiota by enriching\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    and\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    while suppressing opportunistic pathogens. This study integrates targeted delivery, antioxidant therapy, and microbiota modulation, offering an effective strategy for precision IBD treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202524174","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T19:03:41Z","timestamp":1775156621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction of a MOF\u2010Based Snap\u2010Top Delivery Nanosystem for Powerful Dual\u2010Responsive Synergistic Colitis Treatment"],"prefix":"10.1002","volume":"13","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"International Joint Research Laboratory of Nano\u2010Micro Architecture Chemistry College of Chemistry Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy China 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