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.
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.
Nat Nanotechnol. 2024 Aug;19(8):1178-1189. doi: 10.1038/s41565-024-01660-y. Epub 2024 May 13.
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.
糖尿病足溃疡常发生感染，导致治疗并发症增加和肢体丧失风险增加。需要有治疗感染并同时促进愈合的疗法。在这里，我们报告了一种两性脂酶的开发，该脂酶可治疗感染并促进伤口闭合和再上皮化。两性脂酶由用于活性氧 (ROS) 清除的类脂体硒酶组成，以恢复组织氧化还原和免疫稳态。脂酶用于封装光敏剂以进行感染的光动力疗法。我们证明了其在耐甲氧西林金黄色葡萄球菌感染的糖尿病伤口中的应用，该伤口显示出高 ROS 水平，用于光敏剂的抗菌功能和脂酶的纳米酶 ROS 清除以恢复氧化还原和免疫稳态。我们证明了该脂酶可以直接调节巨噬细胞极化并诱导促再生反应。通过单细胞 RNA 测序、T 细胞缺陷 Rag1 小鼠和皮肤浸润免疫细胞分析，我们进一步揭示了产生 IL-17 的 γδ T 细胞对于介导 M1/M2 巨噬细胞转化至关重要。使用脂酶操纵局部免疫稳态可有效促进小鼠和小型猪的皮肤伤口修复和组织再生。
