Accelerating diabetic wound healing by ROSscavenging lipid nanoparticle-mRNA formulation

• 成果类型: Article
• 署名作者: Wang, Siyu; Zhang, Yuebao; Zhong, Yichen; Xue, Yonger; Liu, Zhengwei; Wang, Chang; Kang, Diana D.; Li, Haoyuan; Hou, Xucheng; Tian, Meng; Cao, Dinglingge; Wang, Leiming; Guo, Kaiyuan; Deng, Binbin; Mccomb, David W.; Merad, Miriam; Brown, Brian D.; Abcdefg, Yizhou Dong; Murphy, Catherine
• 署名单位: Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10468
• DOI: 10.1073/pnas.2322935121
• 发表日期: 2024-05-28
• 关键词: growth-factor; angiogenesis; hydrogel; delivery

摘要

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.