Fibronectin-Functionalized Tea Polyphenol Nanoparticles Loaded with Ferrostatin-1 for Synergistic Abdominal Aortic Aneurysms Therapy

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Hongyu Zhang, Bohai Li, Xin Li, Changjiang Yu, Ruixin Fan
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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.

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负载铁他汀-1的纤维连接蛋白功能化茶多酚纳米颗粒协同治疗腹主动脉瘤
腹主动脉瘤(AAA)是一种具有复杂病理生理的危及生命的心血管疾病,目前缺乏有效的药物治疗。近年来,铁下垂已被确定为血管平滑肌细胞(VSMC)死亡的关键机制,并成为缓解主动脉瘤的潜在治疗靶点。本研究开发了一种结合茶多酚基纳米颗粒和铁下垂抑制剂的药物递送纳米颗粒系统。该系统是由表没食子儿茶素没食子酸酯(EGCG)的氧化聚合和自组装形成的,在自组装过程中有效地封装了铁抑素-1 (fe -1),随后被纤维连接蛋白(FN)功能化,用于靶向治疗血管紧张素ii诱导的AAA。体外和体内实验均表明TPN-Fer-1@FN有效抑制铁凋亡,抑制炎症反应,减少基质降解。同时维持VSMCs的正常收缩功能,调节NOTCH3信号通路。此外,TPN-Fer-1@FN纳米体系具有低毒性和良好的生物相容性。这些发现表明TPN-Fer-1@FN是一种很有前景的治疗策略,可以抑制铁下垂和调节AAA的病理过程。
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来源期刊
Advanced Therapeutics
Advanced Therapeutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.10
自引率
2.20%
发文量
130
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