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Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and in\u00a0vivo therapeutic efficacy. The results of our study indicate that the Pcn\/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn\/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient in\u00a0vivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.<\/jats:p>","DOI":"10.34133\/bmr.0062","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T12:20:58Z","timestamp":1720614058000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":19,"title":["Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy"],"prefix":"10.34133","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1152-5496","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7996-4109","authenticated-orcid":false,"given":"Yu","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7074-7945","authenticated-orcid":false,"given":"Luwen","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8455-9749","authenticated-orcid":false,"given":"Zizhen","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7366-7112","authenticated-orcid":false,"given":"Jingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5951-1206","authenticated-orcid":false,"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8455-9749","authenticated-orcid":false,"given":"Kaiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-8866","authenticated-orcid":true,"given":"Cheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-6911","authenticated-orcid":true,"given":"Ningning","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-3763","authenticated-orcid":true,"given":"Shangyong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao, China."},{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"issue":"4","key":"e_1_3_5_2_2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.gtc.2020.07.005","article-title":"Epidemiology and pathogenesis of ulcerative colitis","volume":"49","author":"Du L","year":"2020","unstructured":"Du L, Ha C. 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