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The increased degradation of polyubiquitinated hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) compromises wound healing efficacy. Therefore, the maintenance of HIF\u20101\u03b1 protein stability might help treat DU. Nitric oxide (NO) is an intrinsic biological messenger that functions as a ubiquitination flow repressor and antibacterial agent; however, its clinical application in DU treatment is hindered by the difficulty in controlling NO release. Here, an intelligent near\u2010infrared (NIR)\u2010triggered NO nanogenerator (SNP@MOF\u2010UCNP@ssPDA\u2010Cy7\/IR786s, abbreviated as SNP@UCM) is presented. SNP@UCM represses ubiquitination\u2010mediated proteasomal degradation of HIF\u20101\u03b1 by inhibiting its interaction with E3 ubiquitin ligases under NIR irradiation. Increased HIF\u20101\u03b1 expression in endothelial cells by SNP@UCM enhances angiogenesis in wound sites, promoting vascular endothelial growth factor (VEGF) secretion and cell proliferation and migration. SNP@UCM also enables early detection of wound infections and ROS\u2010mediated killing of bacteria. The potential clinical utility of SNP@UCM is further demonstrated in infected full\u2010thickness DU model under NIR irradiation. SNP@UCM is the first reported HIF\u20101\u03b1\u2010stabilizing advanced nanomaterial, and further materials engineering might offer a facile, mechanism\u2010based method for clinical DU management.<\/jats:p>","DOI":"10.1002\/adma.202103593","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T05:10:57Z","timestamp":1632373857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Ubiquitination Flow Repressors: Enhancing Wound Healing of Infectious Diabetic Ulcers through Stabilization of Polyubiquitinated Hypoxia\u2010Inducible Factor\u20101\u03b1 by Theranostic Nitric Oxide Nanogenerators"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-9967","authenticated-orcid":false,"given":"Yiqi","family":"Yang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants Department of Orthopaedic Surgery Shanghai Ninth 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