Abstract：
After orthopedic surgeries, such as hip replacement, many patients are prone to developing deep vein thrombosis (DVT), which in severe cases can lead to fatal pulmonary embolism or major bleeding. Clinical intervention with high-dose anticoagulant therapy inevitably carries the risk of bleeding. Therefore, a targeted drug delivery system that adjusts local DVT lesions and potentially reduces drug dosage and toxic side effects important. In this study, we developed a targeted drug delivery platelet-derived nanoplatform (AMSNP@PM-rH/A) for DVT treatment that can simultaneously deliver a direct thrombin inhibitor (DTI) Recombinant Hirudin (rH), and the Factor Xa inhibitor Apixaban (A) by utilizing Aminated mesoporous silica nanoparticles (AMSNP). This formulation exhibits improved biocompatibility and blood half-life and can effectively eliminate deep vein thrombosis lesions and achieve therapeutic effects at half the dosage. Furthermore, we employed various visualization techniques to capture the targeted accumulation and release of a platelet membrane (PM) coating in deep vein thrombosis and explored its potential targeting mechanism.
摘要：
骨科手术后,比如髋关节置换,许多患者容易发生深静脉血栓(DVT),在严重的情况下可能导致致命的肺栓塞或大出血。大剂量抗凝治疗的临床干预不可避免地会带来出血的风险。因此,靶向药物递送系统，调整局部DVT病变，并潜在地减少药物剂量和毒副作用。在这项研究中,我们开发了用于DVT治疗的靶向药物递送血小板衍生纳米平台（AMSNP@PM-rH/A），可以同时递送直接凝血酶抑制剂（DTI）重组水蛭素（rH），和因子Xa抑制剂阿哌沙班(A)通过利用氨基化介孔二氧化硅纳米颗粒(AMSNP)。该制剂表现出改善的生物相容性和血液半衰期,并且可以有效地消除深静脉血栓形成病变,并以一半的剂量实现治疗效果。此外，我们采用各种可视化技术来捕获深静脉血栓形成中血小板膜(PM)涂层的靶向积累和释放,并探索其潜在的靶向机制.
