Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle–mRNA formulation

Siyu Wang, Yuebao Zhang, Yichen Zhong, Yonger Xue, Zhengwei Liu, Chang Wang, Diana D. Kang, Haoyuan Li, Xucheng Hou, Meng Tian, Dinglingge Cao, Leiming Wang, Kaiyuan Guo, Binbin Deng, David W. McComb, Miriam Merad, Brian D. Brown, Yizhou Dong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere2322935121
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number22
DOIs
StatePublished - 28 May 2024

Keywords

  • ROS-scavenging lipid
  • lipid nanoparticle–mRNA formulation
  • wound healing

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