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抗氧化和免疫调节聚合物囊泡通过清除 ROS 和免疫调节实现有效的糖尿病伤口治疗。

Antioxidant and Immunomodulatory Polymer Vesicles for Effective Diabetic Wound Treatment through ROS Scavenging and Immune Modulating.

机构信息

Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.

Department of Gynaecology and Obstetrics, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.

出版信息

Nano Lett. 2024 Aug 7;24(31):9494-9504. doi: 10.1021/acs.nanolett.4c01869. Epub 2024 Jul 26.

DOI:10.1021/acs.nanolett.4c01869
PMID:39058893
Abstract

Chronic diabetic wound patients usually show high glucose levels and systemic immune disorder, resulting in high reactive oxygen species (ROS) levels and immune cell dysfunction, prolonged inflammation, and delayed wound healing. Herein, we prepared an antioxidant and immunomodulatory polymer vesicle for diabetic wound treatment. This vesicle is self-assembled from poly(ε-caprolactone)--poly[lysine--(lysine-mannose)--tyrosine)] ([PCL--P[Lys--(Lys-Man)--Tyr]). Polytyrosine is an antioxidant polypeptide that can scavenge ROS. d-Mannose was introduced to afford immunomodulatory functions by promoting macrophage transformation and Treg cell activation through inhibitory cytokines. The mice treated with polymer vesicles showed 23.7% higher Treg cell levels and a 91.3% higher M2/M1 ratio than those treated with PBS. Animal tests confirmed this vesicle accelerated healing and achieved complete healing of -infected diabetic wounds within 8 days. Overall, this is the first antioxidant and immunomodulatory vesicle for diabetic wound healing by scavenging ROS and regulating immune homeostasis, opening new avenues for effective diabetic wound healing.

摘要

慢性糖尿病伤口患者通常表现出高血糖水平和全身免疫紊乱,导致活性氧(ROS)水平升高和免疫细胞功能障碍、炎症持续时间延长以及伤口愈合延迟。在此,我们为糖尿病伤口治疗制备了一种抗氧化和免疫调节聚合物囊泡。这种囊泡由聚(ε-己内酯)-聚[赖氨酸-(赖氨酸甘露糖)-酪氨酸]([PCL-P[Lys-(Lys-Man)-Tyr])自组装而成。聚酪氨酸是一种抗氧化多肽,可通过清除 ROS 发挥作用。通过促进巨噬细胞转化和 Treg 细胞激活,引入 d-甘露糖可提供免疫调节功能,通过抑制性细胞因子。与 PBS 处理的小鼠相比,用聚合物囊泡处理的小鼠 Treg 细胞水平高 23.7%,M2/M1 比值高 91.3%。动物试验证实,这种囊泡可加速愈合,并在 8 天内使感染的糖尿病伤口完全愈合。总的来说,这是第一个通过清除 ROS 和调节免疫稳态来治疗糖尿病伤口愈合的抗氧化和免疫调节囊泡,为有效治疗糖尿病伤口开辟了新途径。

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