2. Academic Validation
  3. Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds

  • Nat Nanotechnol. 2024 May 13. doi: 10.1038/s41565-024-01660-y.
Tingting Wei # 1,  Tiezheng Pan # 1,  Xiuping Peng # 1,  Mengjuan Zhang # 1,  Ru Guo 1,  Yuqing Guo 1,  Xiaohan Mei 1,  Yuan Zhang 1,  Ji Qi 1,  Fang Dong 1,  Meijuan Han 1,  Fandi Kong 1,  Lina Zou 1,  Dan Li 1,  Dengke Zhi 1,  Weihui Wu 1,  Deling Kong 1,  Song Zhang 2 3 4,  Chunqiu Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education and College of Life Sciences, Institute of Transplantation Medicine, Nankai University, Tianjin, China.
  • 2 State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education and College of Life Sciences, Institute of Transplantation Medicine, Nankai University, Tianjin, China. z@immlab.org.
  • 3 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China. z@immlab.org.
  • 4 Institute for Immunology, Nankai University, Tianjin, China. z@immlab.org.
  • 5 State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education and College of Life Sciences, Institute of Transplantation Medicine, Nankai University, Tianjin, China. zhangcq@nankai.edu.cn.
  • # Contributed equally.
PMID: 38740936 DOI: 10.1038/s41565-024-01660-y
Abstract

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage Infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for Reactive Oxygen Species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for Antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA Sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune Cell Analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

Figures
Products