Li Yuanfeng, Du Kaiyi, Peng Danfeng, Zhang Xuanlong, Piao Yinzi, Peng Mengna, He Wei, Wang Yumeng, Wu Haoyue, Liu Yong, Xiao Jian, Shi Linqi, Li Dongdong
Translational Medicine Laboratory, Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Translational Medicine Laboratory, Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Biomaterials. 2025 Nov;322:123411. doi: 10.1016/j.biomaterials.2025.123411. Epub 2025 May 13.
Diabetic wound healing poses a significant clinical challenge with limited therapeutic efficacy due to uncontrolled reactive oxygen species (ROS), inflammatory responses, and extracellular matrix (ECM) degradation caused by abnormal macrophage activity in the wound microenvironment. To address these concerns, we propose a novel formulation that combines Tempo-conjugated lipid with the commercially cationic lipid DOTAP to expedite diabetic wound healing through targeted siRNA delivery (cLpT@siRNA) and restoration of the wound microenvironment. The developed cLpT@siRNA nanocomplexes effectively scavenge excessive ROS levels, facilitate polarization of proinflammatory M1 macrophages towards an anti-inflammatory M2 phenotype, and suppress MMP9 gene expression in macrophages. In the ICR mouse model of diabetic wounds, cLpT@siRNA nanocomplexes significantly accelerate wound healing, promoting neovascularization and collagen deposition. Overall, the cLpT@siRNA nanocomplexes based on antioxidant and cationic lipids provide a promising strategy for delivering siRNA in diabetic wound treatment and hold great potential for clinical translation.
糖尿病伤口愈合是一项重大的临床挑战，由于伤口微环境中巨噬细胞活性异常导致活性氧（ROS）不受控制、炎症反应以及细胞外基质（ECM）降解，治疗效果有限。为了解决这些问题，我们提出了一种新型制剂，将Tempo共轭脂质与市售阳离子脂质DOTAP相结合，通过靶向递送siRNA（cLpT@siRNA）和恢复伤口微环境来加速糖尿病伤口愈合。所开发的cLpT@siRNA纳米复合物可有效清除过量的ROS水平，促进促炎M1巨噬细胞向抗炎M2表型极化，并抑制巨噬细胞中MMP9基因的表达。在糖尿病伤口的ICR小鼠模型中，cLpT@siRNA纳米复合物显著加速伤口愈合，促进新血管形成和胶原蛋白沉积。总体而言，基于抗氧化剂和阳离子脂质的cLpT@siRNA纳米复合物为糖尿病伤口治疗中的siRNA递送提供了一种有前景的策略，具有很大的临床转化潜力。
Proc Natl Acad Sci U S A. 2024-5-28
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