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U.S.A."],"published-print":{"date-parts":[[2024,5,28]]},"abstract":"<jats:p>Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy to accelerate diabetic wound healing by repairing and reprogramming the microenvironment of the wounds. A library of reactive oxygen species (ROS)-responsive TS LNPs was designed and developed to encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at the wound site and induces the expression of IL4 in macrophages, promoting the polarization from the proinflammatory M1 to the anti-inflammatory M2 phenotype at the wound site. In a diabetic wound model of db\/db mice, treatment with this formulation significantly accelerates wound healing by enhancing the formation of an intact epidermis, angiogenesis, and myofibroblasts. Overall, this TS LNP-mRNA platform not only provides a safe, effective, and convenient therapeutic strategy for diabetic wound healing but also holds great potential for clinical translation in both acute and chronic wound care.<\/jats:p>","DOI":"10.1073\/pnas.2322935121","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T13:47:30Z","timestamp":1716299250000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":66,"title":["Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle\u2013mRNA formulation"],"prefix":"10.1073","volume":"121","author":[{"given":"Siyu","family":"Wang","sequence":"first","affiliation":[{"name":"Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029"},{"name":"Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029"},{"name":"Department of Immunology and 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