Local delivery of siRNA using lipid-based nanocarriers with ROS-scavenging ability for accelerated chronic wound healing in diabetes

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-05-13 DOI:10.1016/j.biomaterials.2025.123411

Yuanfeng Li , Kaiyi Du , Danfeng Peng , Xuanlong Zhang , Yinzi Piao , Mengna Peng , Wei He , Yumeng Wang , Haoyue Wu , Yong Liu , Jian Xiao , Linqi Shi , Dongdong Li

{"title":"Local delivery of siRNA using lipid-based nanocarriers with ROS-scavenging ability for accelerated chronic wound healing in diabetes","authors":"Yuanfeng Li , Kaiyi Du , Danfeng Peng , Xuanlong Zhang , Yinzi Piao , Mengna Peng , Wei He , Yumeng Wang , Haoyue Wu , Yong Liu , Jian Xiao , Linqi Shi , Dongdong Li","doi":"10.1016/j.biomaterials.2025.123411","DOIUrl":null,"url":null,"abstract":"<div><div>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 (cL<em>p</em>T@siRNA) and restoration of the wound microenvironment. The developed cL<em>p</em>T@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, cL<em>p</em>T@siRNA nanocomplexes significantly accelerate wound healing, promoting neovascularization and collagen deposition. Overall, the cL<em>p</em>T@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.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123411"},"PeriodicalIF":12.8000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0142961225003308","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

使用具有ros清除能力的脂基纳米载体局部递送siRNA加速糖尿病慢性伤口愈合

由于伤口微环境中巨噬细胞活性异常引起的活性氧（ROS）、炎症反应和细胞外基质（ECM）降解不受控制，糖尿病伤口愈合面临着巨大的临床挑战，治疗效果有限。为了解决这些问题，我们提出了一种新的配方，将tempo共轭脂质与商业阳离子脂质DOTAP结合起来，通过靶向siRNA递送（cLpT@siRNA）和伤口微环境的恢复来加速糖尿病伤口愈合。开发的cLpT@siRNA纳米复合物有效清除过量的ROS水平，促进促炎M1巨噬细胞向抗炎M2表型极化，抑制巨噬细胞中MMP9基因的表达。在糖尿病创面ICR小鼠模型中，cLpT@siRNA纳米复合物显著加速创面愈合，促进新生血管和胶原沉积。总之，基于抗氧化和阳离子脂质的cLpT@siRNA纳米复合物为在糖尿病伤口治疗中递送siRNA提供了一种很有前景的策略，并具有很大的临床翻译潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.