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Diabetic foot ulcers often become infected, leading to treatment complications and an increased risk of limb loss. Treatments are needed to control the infection and promote healing at the same time.
On May 13, 2024, Zhang Chunqiu and Zhang Song (Tingting Wei is the first author) of Nankai University jointly published a research paper entitled "Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds" online in Nature Nanotechnology. The study studies the development of Janus lipidase, which treats infections and promotes wound healing and re-epithelialization. Janus lipidase consists of liposomal like selenoenzymes that are used to scavenge reactive oxygen species (ROS) and restore tissue redox and immunohomeostasis. Liposases are used to encapsulate photosensitizers for photodynamic therapy of infections. The study demonstrated application in methicillin-resistant Staphylococcus aureus infected diabetic wounds, showing antimicrobial function with high ROS levels, ROS clearance from photosensitizers and nanozymes, restoration of redox and immunohomeostasis from lipidases.
This study demonstrates that lipidase can directly regulate macrophage polarization and induce a pro-regenerative response. Single-cell RNA sequencing, analysis of T cell-deficient Rag1−/− mice and skin-infiltrating immune cells further revealed that IL-17-producing γδ T cells play a key role in mediating M1/M2 macrophage transformation. The use of lipidase to control local immunohomeostasis is effective for skin wound repair and tissue regeneration in mice and miniature pigs. Overall, the study provides a promising strategic path for the treatment of DFIs and other acute or chronic wound infections such as venous ulcers, burns, and implant-related infections.
Diabetic foot ulcer is a major complication of diabetes, which seriously affects the quality of life of patients and brings huge clinical and economic burden to patients. Notably, one of the major clinical challenges of diabetic foot ulcers is their susceptibility to hyperglycemia and hypoxic wound tissue helper bacteria, as well as decreased immune cell function and inability to control invading pathogens. This condition leads to diabetic foot infections (DFIs), which are the main cause of lower limb amputation, and in turn, high bacterial load and elevated levels of reactive oxygen species (ROS) cause a persistent inflammatory response, exacerbating the disorder of immune homeostasis, further hindering collagen deposition, neovascularization, and reepithelialization. Animal models and clinical practice have shown that established therapeutic strategies include bioengineered skin, with growth factor, antioxidant, and antimicrobial treatments focusing only on monotherapy with little benefit. Therefore, the development of integrative therapeutics, while eradicating bacteria, remodeling redox and immune homeostasis, is essential for the treatment of DFI.
MRSA感染的糖尿病伤口的程序化调节过程（Credit: Nature Nanotechnology）
The study developed an example of Janus lipase TSeL to promote the healing process of infected diabetic wounds in a programmed manner. Early in treatment, white light irradiation activates the photosensitizer TDTM in TSeL, and rapidly generated reactive oxygen species eradicate bacterial invasion in diabetic wounds. After that, the GPX-like lipase SeL in TSeL exerts its antioxidant function, scavenges ROS, and alleviates oxidative stress. SeL regulates immune homeostasis by inducing macrophage polarization from the M1 (pro-inflammatory) to the M2 (anti-inflammatory) phenotype through direct interactions and γδ T-cell-dependent pathways. The programmed process promotes re-epithelialization and scar-free skin regeneration. Overall, the study provides a promising strategic path for the treatment of DFIs and other acute or chronic wound infections such as venous ulcers, burns, and implant-related infections.
Original link https://www.nature.com/articles/s41565-024-01660-y
Editor-in-charge|Explore Jun
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文章来源|“ iNature”
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