Coronary Stents Decorated by Heparin/NONOate Nanoparticles for Anticoagulant and Endothelialized Effects

Coronary Stents Decorated by Heparin/NONOate Nanoparticles for Anticoagulant and Endothelialized Effects
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肝素/NONOate 纳米颗粒装饰的冠状动脉支架具有抗凝和内皮化作用

DOI:
10.1021/acs.langmuir.0c00112
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发表时间:
2020
期刊:
影响因子:
3.9
通讯作者:
Shen Jian
Shen Jian
中科院分区:
化学2区
文献类型:
--
作者:
Zhu Tianyu;Zhou Min;Gao Wentao;Fang Dan;Liu Zhiyong;Wu Guangyan;Wan Mimi;Mao Chun;Shen Jian

文献摘要

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在冠状动脉疾病(CAD)的治疗中,支架植入术的使用经常导致临床并发症,如再狭窄、延迟内皮愈合和血栓形成。在此,我们通过接枝肝素/NONOates纳米颗粒(Hep/NONOates)为支架表面开发了一种双药物缓释涂层。采用X射线光电子能谱、衰减全反射傅里叶变换红外光谱、静态水接触角、扫描电镜等方法对Hep/NONOates及支架表面改性进行表征,并研究抗凝剂肝素(Hep)和生物活性分子一氧化氮(NO)的释放行为。通过全血粘附试验、血小板粘附试验、溶血试验、红细胞形态学变化、血浆凝固时间试验、体外凝固时间试验和MTT法评价了改性支架的血液相容性和细胞毒性。最后,兔颈动脉支架植入实验结果表明,该支架的双药物缓释涂层能够加速内皮细胞的再生,并保持良好的抗凝活性。本研究可为提高药物洗脱支架的安全性和有效性提供基于纳米技术的新设计思路。
In the treatment of coronary artery disease (CAD), the use of stent implantation often leads to clinical complications such as restenosis, delayed endothelial healing, and thrombosis. Here, we develop a double drug sustained-release coating for the stent surface by grafting heparin/NONOate nanoparticles (Hep/NONOates). The Hep/NONOates and surface modification of the stent were characterized by X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, static water contact angle, and scanning electron microscopy (SEM), and the release behaviors of the anticoagulant, heparin (Hep) and the bioactive molecule, nitric oxide (NO) were studied. Furthermore, the blood compatibility and cytotoxicity of the modified stent were evaluated by whole blood adhesion and platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, plasma recalcification time assay,in vitrocoagulation time tests, and MTT assay. Finally, the results of a rabbit carotid artery stent implantation experiment showed that the double drug sustained-release coating for the stent can accelerate regeneration of endothelial cells and keep good anticoagulant activity. This study can provide new design ideas based on nanotechnology for improving the safety and effectiveness of drug-eluting stents.