{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:50:03Z","timestamp":1791373803945,"version":"4.3.1"},"reference-count":240,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammatory bowel disease (IBD), encompassing Crohn\u2019s disease and ulcerative colitis, is a chronic relapsing inflammatory disorder that increases the risk of colitis-associated colorectal cancer (CAC). Despite major advances in biologics and small-molecule therapies, many patients experience primary or secondary treatment failure, adverse effects, and disease recurrence, underscoring the need for more effective, targeted therapeutic strategies. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, have emerged as promising nanoscale therapeutic platforms owing to their intrinsic biocompatibility, low immunogenicity, cargo-protective lipid bilayer, and natural ability to mediate intercellular communication. Recent advances in EV engineering have further expanded their therapeutic potential through genetic modification of parental cells, cargo loading, surface functionalization, and hybrid biomaterial systems, enabling enhanced targeting, drug delivery, immune modulation, tissue regeneration, and anti-tumor activity. This review summarizes the biological characteristics of EVs and discusses recent progress in engineering strategies aimed at improving their therapeutic efficacy in IBD and CAC. We critically evaluate current preclinical evidence regarding immunomodulation, restoration of intestinal barrier integrity, regulation of gut microbiota, targeted drug delivery, cancer immunotherapy, and inhibition of metastasis. Finally, we discuss the major translational challenges, including manufacturing standardization, quality control, large-scale production, safety evaluation, regulatory considerations, and future perspectives necessary for successful clinical implementation of engineered EV-based therapies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1933602","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:55:41Z","timestamp":1791370541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering extracellular vesicles for inflammatory bowel disease and colitis-associated colorectal cancer: from therapeutic innovation to clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Minrui","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Yuan","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Muro","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Endoscopy, The Affiliated Yixing Hospital of Jiangsu University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Clinical Medicine and Laboratory Medicine, Jiangsu University","place":["Zhenjiang, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second People's Hospital of Lianyungang","place":["Lianyungang, China"]},{"name":"Department of Laboratory Medicine, Affiliated Lianyungang Clinical College of Jiangsu University","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5a","DOI":"10.1155\/2005\/269076","article-title":"Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology","volume":"19","author":"Silverberg","year":"2005","journal-title":"Can J Gastroenterol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1201\/b14283-52","article-title":"Progress in the diagnosis and treatment of inflammatory bowel disease","volume":"7","author":"Loftus","year":"2011","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: current state of the art","volume":"13","author":"de Souza","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12328-017-0813-5","article-title":"Gut microbiota in the pathogenesis of inflammatory bowel disease","volume":"11","author":"Nishida","year":"2018","journal-title":"Clin J Gastroenterol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.07.042","article-title":"Extraintestinal manifestations of inflammatory bowel disease: current concepts, treatment, and implications for disease management","volume":"161","author":"Rogler","year":"2021","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12081839","article-title":"Extraintestinal manifestations in inflammatory bowel disease: from pathophysiology to treatment","volume":"12","author":"Faggiani","year":"2024","journal-title":"Biomedicines"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx008","article-title":"Third European evidence-based consensus on diagnosis and management of ulcerative colitis. 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