纤维蛋白靶向和H <sub>2</sub> O <sub>2</sub>响应纳米颗粒作为血栓形成血管的治疗诊断学。,ACS Nano

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纤维蛋白靶向和H ₂ O ₂响应纳米颗粒作为血栓形成血管的治疗诊断学。
ACS Nano ( IF 15.8 ) Pub Date : 2017-05-08 00:00:00 , DOI: 10.1021/acsnano.7b02308
Changsun Kang , Sian Gwon , ChulGyu Song , Peter M. Kang ₁ , Seong-Cheol Park ₂ , Jongho Jeon ₃ , Do Won Hwang ₄ , Dongwon Lee

Affiliation

在受伤的血管中形成血栓（血凝块），以维持脉管系统的完整性。然而，由于血栓形成而阻塞血管会减慢血液流动，导致动脉供血的组织死亡，并且是各种威胁生命的心血管疾病的罪魁祸首。在本文中，我们报告了合理设计的纳米药物，该药物可以对阻塞的血管进行特殊成像并抑制血栓形成。根据血栓的理化和生物学特性，例如丰富的血纤蛋白和过高的过氧化氢（H ₂ O ₂）水平，我们开发了针对血纤蛋白的成像和抗血栓性纳米药物，称为FTIAN，作为治疗该病的治疗方法阻塞性血栓形成。FTIAN抑制了H ₂ O的生成₂和抑制肿瘤坏死因子-α（TNF-α）和可溶性CD40配体（sCD40L）在活化的血小板中的表达，表明其固有的抗氧化剂，抗炎和抗血小板活性。在氯化铁（FeCl ₃）诱导的颈动脉血栓形成的小鼠模型中，FTIAN专门靶向阻塞性血栓并显着增强了荧光/光声信号。当装载抗血小板药物替罗非班时，FTIAN显着抑制了血栓形成。鉴于其血栓特异性成像以及出色的治疗活性，FTIAN作为阻塞性血栓形成的纳米治疗剂具有巨大的翻译潜力。

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Fibrin-Targeted and H2O2-Responsive Nanoparticles as a Theranostics for Thrombosed Vessels

A thrombus (blood clot) is formed in injured vessels to maintain the integrity of vasculature. However, obstruction of blood vessels by thrombosis slows blood flow, leading to death of tissues fed by the artery and is the main culprit of various life-threatening cardiovascular diseases. Herein, we report a rationally designed nanomedicine that could specifically image obstructed vessels and inhibit thrombus formation. On the basis of the physicochemical and biological characteristics of thrombi such as an abundance of fibrin and an elevated level of hydrogen peroxide (H₂O₂), we developed a fibrin-targeted imaging and antithrombotic nanomedicine, termed FTIAN, as a theranostic system for obstructive thrombosis. FTIAN inhibited the generation of H₂O₂ and suppressed the expression of tumor necrosis factor-alpha (TNF-α) and soluble CD40 ligand (sCD40L) in activated platelets, demonstrating its intrinsic antioxidant, anti-inflammatory, and antiplatelet activity. In a mouse model of ferric chloride (FeCl₃)-induced carotid thrombosis, FTIAN specifically targeted the obstructive thrombus and significantly enhanced the fluorescence/photoacoustic signal. When loaded with the antiplatelet drug tirofiban, FTIAN remarkably suppressed thrombus formation. Given its thrombus-specific imaging along with excellent therapeutic activities, FTIAN offers tremendous translational potential as a nanotheranostic agent for obstructive thrombosis.

更新日期：2017-05-19

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