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To protect against gastrointestinal degradation and promote penetration across the intestinal mucosa, a pH\u2010triggered self\u2010unpacking capsule encapsulating zwitterionic hydrogel\u2010coated metal\u2010organic framework (MOF) nanoparticles is engineered. The MOF nanoparticles possess a high exendin\u20104 loading capacity, and the zwitterionic hydrogel layer imparts unique capability of permeation across the mucus layer and effective internalization by epithelial cells to the nano\u2010vehicles. In addition to the gastro\u2010resistant feature, the pH\u2010responsive capsules are dissociated drastically in the intestinal environment due to the rapid generation of abundant CO\n                    <jats:sub>2<\/jats:sub>\n                    bubbles, which triggers a sudden release of the nanoparticles. After oral administration of the capsules containing exendin\u20104\u2010loaded nanoparticles into a diabetes rat model, markedly enhanced plasma exendin\u20104 levels are achieved for over 8 h, leading to significantly increased endogenous insulin secretion and a remarkable hypoglycemic effect with a relative pharmacological availability of 17.3%. Owing to the low risk of hypoglycemia, this oral exendin\u20104 strategy will provide a vast potential for daily and facile diabetes treatment.\n                  <\/jats:p>","DOI":"10.1002\/adma.202102044","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T11:00:30Z","timestamp":1625310030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["A pH\u2010Triggered Self\u2010Unpacking Capsule Containing Zwitterionic Hydrogel\u2010Coated MOF Nanoparticles for Efficient Oral Exendin\u20104 Delivery"],"prefix":"10.1002","volume":"33","author":[{"given":"Yuhao","family":"Zhou","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun 130022 China"},{"name":"University of Science and Technology of China  Hefei Anhui 230026 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