Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

中文翻译：

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血栓微环境响应性交联环糊精金属有机骨架纳米载体用于精确靶向和溶栓

由于血栓性疾病的高死亡率和致残率，全球公共健康受到血栓性疾病的严重威胁。大多数溶栓剂，尤其是蛋白质药物，在循环中的半衰期较短，从而降低了其溶栓效果。创建智能药物输送系统，精确输送药物并在附近血栓部位的调节条件下释放药物，对于有效溶栓至关重要。在本文中，我们提出了一种独特的药物输送系统（MCRUA），该系统选择性地靶向血小板并​​通过血栓微环境的刺激释放药物。血栓溶解酶尿激酶型纤溶酶原激活剂 (uPA) 和抗炎药物阿司匹林（乙酰水杨酸，ASA）均负载到组成 MCRUA 系统的 pH 敏感 CaCO3/环糊精交联金属有机框架 (MC) 上。 c(RGD)在MC表面进行功能化，通过RGD功能化进行酯化反应。此外，血栓部位的酸性微环境会导致 MCRUA 崩解，释放出 uPA，用于溶栓并帮助血管再通。此外，环糊精包裹的ASA能够治疗血栓内的炎症环境，增强抗血小板聚集作用，促进协同溶栓治疗。当用于血栓性疾病时，我们的药物输送系统 (MCRUA) 可促进溶栓、抑制再血栓形成并增强生物安全性，同时减少出血副作用。