基于二维材料黑磷的新型MNP&αIIbβ3受体双重介导的尿激酶递释平台联合光热疗法靶向溶栓研究

深静脉血栓形成（DVT）已严重危害人类健康。目前用于溶栓的药物存在血浆半衰期短、靶向性差、过量使用易引发出血等缺点。因此，迫切需要提高溶栓的靶向性。纳米给药是目前研究最多的新型给药方法，它可以改变药物的药代动力学特征，提高药物的生物利用度。新型纳米材料——黑磷（BP）因光热转换率高，载药量大，生物相容性好而广泛用于生物医学领域。本课题组前期研究发现磁性纳米粒（MNP）在磁场中能使药物载体定向运动，并且光热疗法能增强溶栓效果。本项目拟构建双重靶向溶栓药物载体并联合近红外光用于精准溶栓：将能与血小板GPⅡb/Ⅲa受体特异性结合的αIIbβ3及MNP修饰到BP纳米片表面以制出兼具受体和磁介导靶向的药物递送平台，并系统探究该载药体系的理化及药理学特性，体内外溶栓的靶向能力及效果。本项目率先用BP纳米片构建双重靶向药物载体并联合近红外光用于精准溶栓，为DVT的治疗提供新思路。

Deep venous thrombosis (DVT) has seriously endangered human health. At present, the drugs used for thrombolysis have some disadvantages, such as short plasma half-life, poor targeting, easy to cause bleeding and so on. Therefore, there is an urgent need to improve the targeting of thrombolysis. Nano-drug delivery is the most widely studied new drug delivery method at present, which can change the pharmacokinetic characteristics of drugs and improve the bioavailability of drugs. Black phosphorus (BP), a new nanomaterial, is widely used in biomedical field because of its high photothermal conversion rate, large drug loading and good biocompatibility. The previous study of our group found that magnetic nanoparticles (MNP) can make drug carriers move directionally in magnetic field, and photothermal therapy can enhance the effect of thrombolysis. In this project, double targeted thrombolytic drug carriers were constructed and combined with near-infrared light for precise thrombolysis: α IIb β 3 and MNP which could specifically bind to platelet GPIb / Ⅲ a receptors were modified onto the surface of BP nanoscales to prepare a drug delivery platform with both receptor and magnetic targeting, and systematically explore the physicochemical and pharmacological properties of the drug delivery system, the targeting ability and effect of thrombolysis in vivo and in vitro. This project is the first to use BP nano-tablets to construct dual targeted drug carriers combined with near-infrared light for accurate thrombolysis, which provides a new idea for the treatment of DVT.