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

doi:10.1073/pnas.232293512

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 journal › Article › peer-review

11 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 language	English
Article number	e2322935121
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	121
Issue number	22
DOIs	https://doi.org/10.1073/pnas.232293512
State	Published - 28 May 2024

Keywords

ROS-scavenging lipid
lipid nanoparticle–mRNA formulation
wound healing

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10.1073/pnas.232293512

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Wang, S., Zhang, Y., Zhong, Y., Xue, Y., Liu, Z., Wang, C., Kang, D. D., Li, H., Hou, X., Tian, M., Cao, D., Wang, L., Guo, K., Deng, B., McComb, D. W., Merad, M., Brown, B. D., & Dong, Y. (2024). Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle–mRNA formulation. Proceedings of the National Academy of Sciences of the United States of America, 121(22), Article e2322935121. https://doi.org/10.1073/pnas.232293512

@article{cfad64a805e7402da835ebde107fb089,

title = "Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle–mRNA formulation",

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.",

keywords = "ROS-scavenging lipid, lipid nanoparticle–mRNA formulation, wound healing",

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

note = "Publisher Copyright: {\textcopyright} 2024 the Author(s). Published by PNAS.",

year = "2024",

month = may,

day = "28",

doi = "10.1073/pnas.232293512",

language = "English",

volume = "121",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

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Wang, S, Zhang, Y, Zhong, Y, Xue, Y, Liu, Z, Wang, C, Kang, DD, Li, H, Hou, X, Tian, M, Cao, D, Wang, L, Guo, K, Deng, B, McComb, DW, Merad, M, Brown, BD & Dong, Y 2024, 'Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle–mRNA formulation', Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 22, e2322935121. https://doi.org/10.1073/pnas.232293512

TY - JOUR

T1 - Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle–mRNA formulation

AU - Wang, Siyu

AU - Zhang, Yuebao

AU - Zhong, Yichen

AU - Xue, Yonger

AU - Liu, Zhengwei

AU - Wang, Chang

AU - Kang, Diana D.

AU - Li, Haoyuan

AU - Hou, Xucheng

AU - Tian, Meng

AU - Cao, Dinglingge

AU - Wang, Leiming

AU - Guo, Kaiyuan

AU - Deng, Binbin

AU - McComb, David W.

AU - Merad, Miriam

AU - Brown, Brian D.

AU - Dong, Yizhou

PY - 2024/5/28

Y1 - 2024/5/28

N2 - 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.

AB - 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.

KW - ROS-scavenging lipid

KW - lipid nanoparticle–mRNA formulation

KW - wound healing

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U2 - 10.1073/pnas.232293512

DO - 10.1073/pnas.232293512

M3 - Article

C2 - 38771877

AN - SCOPUS:85194022581

SN - 0027-8424

VL - 121

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 22

M1 - e2322935121

ER -

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

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Keywords

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