Enalaprilat reverses neutrophil polarization imbalance via targeting taurine-STING axis for treatment of diabetic wounds

  • Cell Rep Med. 2026 Apr 21;7(4):102714. doi: 10.1016/j.xcrm.2026.102714.
Li Lu  1 ,  Yuan Xiong  2 ,  Jiewen Liao  3 ,  Juan Zhou  4 ,  Guangji Wang  5 ,  Yating Qin  6 ,  Shengming Zhang  3 ,  Yanzhi Zhao  3 ,  Xiaodan Zhong  6 ,  Mengwen Wang  6 ,  Kangkang Zha  3 ,  Fawwaz Al-Smadi  3 ,  Guohui Liu  7 ,  Yanli Zhao  8 ,  Bobin Mi  9
Affiliations
  • 1. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2. Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 3. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 4. Department of Cardiology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430073, China.
  • 5. Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430073, China.
  • 6. Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 7. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: [email protected].
  • 8. School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore. Electronic address: [email protected].
  • 9. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore. Electronic address: [email protected].
PMID: 41916295 DOI: 10.1016/j.xcrm.2026.102714
Abstract

Persistent inflammation derived from neutrophil activation drives delayed healing of diabetic wounds. Herein, a dissolvable alginate methacryloyl-based microneedle patch functionalized with polypeptide CFLFLFK-NH2-coupled manganese/zinc ion metal-organic framework (MnZn-MOF) loading enalaprilat (Ena) (TMZE@A-MN) is developed. Ena promotes neutrophil repolarization from pro-inflammatory N1 to anti-inflammatory N2 state by inhibiting nuclear factor (NF)-κB axis and activating SMAD3 pathway, attributed to Ena-induced level elevation of taurine and subsequently STING signaling cascade suppression, thus causing macrophage phenotype switching and endothelial cell Ferroptosis repression. Due to identifiable property of CFLFLFK-NH2 on neutrophil membrane receptors, the delivery system endows Ena with targeting inhibitory roles in neutrophil activation. In addition, MnZn-MOFs possess free radical-eliminating performance and can effectively combat the growth of methicillin-resistant Staphylococcus aureus and Escherichia coli. In vivo evaluation on diabetic murine and porcine wounds also demonstrates that the TMZE@A-MN accelerates wound healing process. Consequently, the targeted microneedle delivery system holds great promise for diabetic wound treatment.

Keywords
diabetic wound; enalaprilat; metal-organic framework; microneedle; neutrophil.
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