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Herein, a nanoscale complex combining both electrostatic\u2010 and dynamic\u2010covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high\u2010affinity glucose\u2010binding motif yields an injectable insulin depot affording both glucose\u2010directed and long\u2010lasting insulin availability. Following a single injection, it is even possible to control blood glucose for at least one week in diabetic swine subjected to daily oral glucose challenges. Measurements of serum insulin concentration in response to challenge show increases in insulin corresponding to elevated blood glucose levels, an uncommon finding even in preclinical work on glucose\u2010responsive insulin. Accordingly, the subcutaneous nanocomplex that results from combining electrostatic\u2010 and dynamic\u2010covalent interactions between a modified insulin and a synthetic dendrimer carrier affords a glucose\u2010responsive insulin depot for week\u2010long control following a single routine injection.<\/jats:p>","DOI":"10.1002\/adma.202308965","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:27:47Z","timestamp":1700738867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Insulin\u2013Dendrimer Nanocomplex for Multi\u2010Day Glucose\u2010Responsive Therapy in Mice and Swine"],"prefix":"10.1002","volume":"36","author":[{"given":"Sijie","family":"Xian","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering  105 McCourtney Hall Notre Dame IN 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhui","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; 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