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基于依布硒啉的活性氧物种响应性涂层:用于心血管支架表面改性的抗氧化、促内皮化和抗增殖作用

Reactive oxygen species-responsive coating based on Ebselen: Antioxidation, pro-endothelialization and anti-hyperplasia for surface modification of cardiovascular stent.

作者信息

Chen Xinyi, Wang Rui, Du Yuhua, Mou Yonghong, Gong Yan, Zhao Xueyu, Li Wenzhong, Li Xin, Wang Jin, Zhao Yuancong

机构信息

College of Medicine, Institute of Biomedical Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.

出版信息

Colloids Surf B Biointerfaces. 2025 Jan;245:114314. doi: 10.1016/j.colsurfb.2024.114314. Epub 2024 Oct 11.

Abstract

Atherosclerosis is often accompanied by inflammation and oxidative stress. Excessive reactive oxygen species (ROS) can damage the vascular endothelium, leading to endothelial dysfunction and reduced nitric oxide (NO) bioavailability. Further accumulation of ROS contributes to vascular cell damage, lipid peroxidation, and extracellular matrix deposition. Thus, clearing excess ROS and reshaping the oxidative microenvironment is essential for treating atherosclerosis (AS). In this study, Ebselen, which mimics glutathione peroxidase and possesses redox capabilities, was successfully synthesized. Subsequently, a multifunctional coating was designed using a combination of Ebselen and poly (trimethylene carbonate) (PTMC), capable of protecting cells from ROS-induced damage, promoting vascular endothelialization, and exhibiting anti-proliferative properties. The Ebselen-loaded coating effectively scavenges free radicals (with an elimination rate of 89 %), catalytically releases NO (0.96 × 10⁻¹⁰ to 1.26 × 10⁻¹⁰ mol/cm²/min), and sustainably delivers Ebselen to the lesion site through a redox cycle. Notably, this coating shows excellent hemocompatibility and cytocompatibility. Subcutaneous implantation results indicated that the fibrous capsule thickness of PTMC10 was the lowest, at just 47.7 % of that of PTMC. Therefore, the Ebselen-loaded coating presents promising applications in cardiovascular stents.

摘要

动脉粥样硬化常伴有炎症和氧化应激。过量的活性氧(ROS)会损伤血管内皮,导致内皮功能障碍和一氧化氮(NO)生物利用度降低。ROS的进一步积累会导致血管细胞损伤、脂质过氧化和细胞外基质沉积。因此,清除过量的ROS并重塑氧化微环境对于治疗动脉粥样硬化(AS)至关重要。在本研究中,成功合成了模拟谷胱甘肽过氧化物酶并具有氧化还原能力的依布硒仑。随后,设计了一种由依布硒仑和聚碳酸三亚甲酯(PTMC)组合而成的多功能涂层,该涂层能够保护细胞免受ROS诱导的损伤,促进血管内皮化,并具有抗增殖特性。负载依布硒仑的涂层能有效清除自由基(清除率为89%),催化释放NO(0.96×10⁻¹⁰至1.26×10⁻¹⁰ mol/cm²/min),并通过氧化还原循环将依布硒仑持续递送至病变部位。值得注意的是,该涂层具有优异的血液相容性和细胞相容性。皮下植入结果表明,PTMC10的纤维囊厚度最低,仅为PTMC的47.7%。因此,负载依布硒仑的涂层在心血管支架方面具有广阔的应用前景。

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