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Although ROS-scavenging therapy holds significant therapeutic potential for the management of IBD, systemic off-target effects remain a major limitation. Recent studies have identified microRNA-497 (miR-497) as a promising therapeutic target for IBD as it can polarize proinflammatory M1 macrophages to a tissue-repair phenotype, promoting the clearance of ROS and potentially alleviating the symptoms of IBD. Despite its therapeutic potential, the poor stability and limited cellular uptake of miR-497 pose significant barriers to its clinical use. To address these limitations, a delivery strategy based on manganese-doped metal\u2212organic framework (Mn-MOF) nanoparticles labeled with miR-497 (Mn-MOF@miR-497) was developed to effectively inhibit the production of proinflammatory cytokines and restore immunological tolerance in enterocytes disrupted by proinflammatory stimuli. The topical administration of Mn-MOF@miR-497 exhibited significant therapeutic efficacy in a murine model of IBD induced by dextran sulfate sodium (DSS) without any observable toxicity. This innovative nanotherapeutic strategy demonstrates remarkable potential as a targeted treatment approach for IBD, holding promise for exploring innovative therapeutic regimens for IBD management.<\/jats:p>","DOI":"10.1021\/acsami.6c11703","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:17:32Z","timestamp":1784564252000},"page":"40566-40575","source":"Crossref","is-referenced-by-count":0,"title":["Orally Delivered Nanotherapeutics with miRNA-497 Supplying for Inflammatory Bowel Disease"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-6705","authenticated-orcid":true,"given":"Hanlin","family":"Liu","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Mu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Shi","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suye","family":"Ran","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Yao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Xingyi People's Hospital , , ,","place":["Xingyi, China, 562400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-1356","authenticated-orcid":true,"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]},{"name":"Affiliated Hospital of Guizhou Medical University , , ,","place":["Guiyang, China, 550004"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"2026080612062553500_cit1","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1056\/NEJMra2002697","article-title":"Pathophysiology of Inflammatory Bowel Diseases","volume":"383","author":"Chang","year":"2020","journal-title":"N. 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