Hongyu Zhang, Bohai Li, Xin Li, Changjiang Yu, Ruixin Fan
{"title":"Fibronectin-Functionalized Tea Polyphenol Nanoparticles Loaded with Ferrostatin-1 for Synergistic Abdominal Aortic Aneurysms Therapy","authors":"Hongyu Zhang, Bohai Li, Xin Li, Changjiang Yu, Ruixin Fan","doi":"10.1002/adtp.202500179","DOIUrl":null,"url":null,"abstract":"<p>Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular condition with complex pathophysiology, for which effective pharmacological treatments are currently lacking. Recently, ferroptosis has been identified as a key mechanism of vascular smooth muscle cell (VSMC) death, emerging as a potential therapeutic target for mitigating aortic aneurysms. Here, a drug-delivery nanoparticle system combining tea polyphenol-based nanoparticles and a ferroptosis inhibitor is developed. This system, formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates Ferrostatin-1 (Fer-1) during self-assembly and is subsequently functionalized with fibronectin (FN) for targeted treatment of angiotensin II-induced AAA. Both in vitro and in vivo experiments demonstrated that TPN-Fer-1@FN effectively inhibits ferroptosis, suppresses the inflammatory response, and reduces matrix degradation, while preserving the normal contractile function of VSMCs and modulating the NOTCH3 signaling pathway. Moreover, the TPN-Fer-1@FN nanosystem exhibited low toxicity and good biocompatibility. These findings suggest that TPN-Fer-1@FN represents a promising therapeutic strategy for inhibiting ferroptosis and modulating the pathological processes underlying AAA.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://advanced.onlinelibrary.wiley.com/doi/10.1002/adtp.202500179","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular condition with complex pathophysiology, for which effective pharmacological treatments are currently lacking. Recently, ferroptosis has been identified as a key mechanism of vascular smooth muscle cell (VSMC) death, emerging as a potential therapeutic target for mitigating aortic aneurysms. Here, a drug-delivery nanoparticle system combining tea polyphenol-based nanoparticles and a ferroptosis inhibitor is developed. This system, formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates Ferrostatin-1 (Fer-1) during self-assembly and is subsequently functionalized with fibronectin (FN) for targeted treatment of angiotensin II-induced AAA. Both in vitro and in vivo experiments demonstrated that TPN-Fer-1@FN effectively inhibits ferroptosis, suppresses the inflammatory response, and reduces matrix degradation, while preserving the normal contractile function of VSMCs and modulating the NOTCH3 signaling pathway. Moreover, the TPN-Fer-1@FN nanosystem exhibited low toxicity and good biocompatibility. These findings suggest that TPN-Fer-1@FN represents a promising therapeutic strategy for inhibiting ferroptosis and modulating the pathological processes underlying AAA.