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Upon oxidation, a dense, stable, and uniform membrane with nanochannels is in situ formed on the surface of insulin crystals, achieving high drug encapsulation efficiency, loading content, and sustained release performance. After further functionalization with 4-carboxy-3-fluorophenylboronic acid (FPBA), the membrane can mediate insulin release in a glucose-responsive manner. Notably, beyond the conventional charge switch induced by the binding between glucose and FPBA, molecular dynamics simulation identifies that glucose binding weakens noncovalent interactions among polymer chains and reduces membrane compactness, thereby accelerating insulin release. A single injection of encapsulated insulin crystals maintains normoglycemia for up to 218 and 190 h, respectively, in type 1 diabetic mouse and minipig models. This formulation also exhibits in vivo glucose-responsive insulin release, low risk of hypoglycemia, biodegradability, and high biocompatibility. This study presents a bioinspired membrane-enclosed strategy for developing long-acting and injectable formulations for hydrophilic drugs.<\/jats:p>","DOI":"10.1021\/jacs.6c07195","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T10:01:37Z","timestamp":1786096897000},"page":"34244-34256","source":"Crossref","is-referenced-by-count":0,"title":["Mussel-Inspired Membrane\nEncapsulation Strategy for\nDeveloping Long-Acting Glucose-Responsive Injectable Insulin Crystals"],"prefix":"10.1021","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3320-7169","authenticated-orcid":true,"given":"Jianchang","family":"Xu","sequence":"first","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College , , ,","place":["Hangzhou, China, 310014"]},{"name":"Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College , , ,","place":["Hangzhou, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Harvard University , , , ,","place":["Cambridge, Massachusetts, United States, 02138"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoujie","family":"Wang","sequence":"additional","affiliation":[{"name":"Hangzhou Medical College , , ,","place":["Hangzhou, China, 311300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen University , , ,","place":["Shenzhen, China, 518060"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangfan","family":"Ji","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ye","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College , , ,","place":["Hangzhou, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-4456","authenticated-orcid":true,"given":"Zhen","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310027"]},{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310016"]},{"name":"Liangzhu Laboratory , ,","place":["Hangzhou, China, 311121"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-838X","authenticated-orcid":true,"given":"Jinqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang University , , ,","place":["Hangzhou, China, 310058"]},{"name":"Jinhua Institute of Zhejiang University , ,","place":["Jinhua, China, 321299"]},{"name":"Zhejiang University School of Medicine, Zhejiang University , , ,","place":["Hangzhou, China, 310009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026081910205716100_cit1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s10126-007-9053-x","article-title":"Understanding marine mussel adhesion","volume":"9","author":"Silverman","year":"2007","journal-title":"Mar. 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