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Nitric oxide (NO), a gaseous mediator with high diffusivity and membrane permeability, is aberrantly overproduced in diverse inflammatory conditions and thus represents a promising trigger for responsive drug delivery. Here, we present a NO\u2010responsive microneedle (NOR\u2010MN) platform that exploits pathological NO for controlled transdermal therapy. The system integrates a NO\u2010cleavable crosslinker that degrades selectively in NO\u2010rich environments, enabling NO\u2010dependent release of encapsulated drugs while simultaneously scavenging excess NO to mitigate inflammation. This dual\u2010functional design combines disease\u2010responsive delivery with intrinsic anti\u2010inflammatory activity, offering a minimally invasive and therapeutically adaptable platform. The therapeutic potential of NOR\u2010MNs was validated in both acute and chronic inflammatory models. In lipopolysaccharide\u2010induced peritonitis, dexamethasone\u2010loaded NOR\u2010MNs achieved NO\u2010triggered release, suppressed cytokine production, alleviated hepatic toxicity, and improved tissue pathology. In diabetes mellitus, insulin\u2010loaded NOR\u2010MNs responded to elevated NO levels to restore glucose homeostasis and enhanced insulin responsiveness in vitro. Collectively, these findings establish NO\u2010responsive microneedles as an innovative stimuli\u2010responsive strategy with broad applicability for the treatment of inflammation\u2010driven diseases.<\/jats:p>","DOI":"10.1002\/adhm.202504714","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:10:27Z","timestamp":1770095427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pathological Nitric Oxide\u2010Triggered Microneedle Patch for Spatiotemporally Controlled Therapy of Acute and Chronic Inflammatory Disorders"],"prefix":"10.1002","volume":"15","author":[{"given":"Sangmin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Chemistry, POSTECH\u2010CATHOLIC Biomedical Engineering Institute Pohang University of Science and Technology (POSTECH) Pohang Gyeongbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonju","family":"Boo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, POSTECH\u2010CATHOLIC Biomedical Engineering Institute Pohang University of Science and Technology (POSTECH) Pohang Gyeongbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SeungHyun","family":"Park","sequence":"additional","affiliation":[{"name":"Major of Human Bioconvergence Division of Smart Healthcare Pukyong National University  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Eom","sequence":"additional","affiliation":[{"name":"Department of Chemistry, POSTECH\u2010CATHOLIC Biomedical Engineering Institute Pohang University of Science and Technology (POSTECH) Pohang Gyeongbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WonHyoung","family":"Ryu","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering Yonsei University  Seodaemun\u2010Gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-0999","authenticated-orcid":false,"given":"Won Jong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, POSTECH\u2010CATHOLIC Biomedical Engineering Institute Pohang University of Science and Technology (POSTECH) Pohang Gyeongbuk Republic of Korea"},{"name":"OmniaMed Co, Ltd.  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