Platelet membrane-functionalized hollow mesoporous Prussian blue nanomedicine for comprehensive thrombolytic management by targeted enhanced fibrinolysis and ROS scavenging
Platelet membrane-functionalized hollow mesoporous Prussian blue nanomedicine for comprehensive thrombolytic management by targeted enhanced fibrinolysis and ROS scavenging
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DOI：
10.1016/j.cej.2023.145515
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发表时间：
2023-08-23
影响因子：
15.1
通讯作者：
Guo，Dajing
中科院分区：
文献类型：
--
作者：
Zhang，Wenli;Sun，Maoyuan;Guo，Dajing
血栓性疾病在世界范围内造成严重的残疾和死亡风险。然而，传统的溶栓药物半衰期短，靶向能力差，治疗效果有限，治疗窗窄。此外，大多数基础研究仅关注溶栓效率，而忽略了促进血栓形成进展的炎症因子，如活性氧（ROS）介导的氧化应激。因此，要实现全面有效的溶栓治疗，必须同时做到靶向溶栓治疗和清除炎症因子。本研究以普鲁士蓝（PB）和阿替普酶（rtPA）两种药物为原料，通过共组装的方法制备了血小板膜功能化的中空介孔普鲁士蓝纳米药物（HMPB-rtPA@PM），该药物在血栓靶向和光热/药物协同纤溶方面具有显著优势。此外，HMPB-rtPA@PM显示出抑制血小板聚集和通过清除ROS调节炎症微环境的潜力。正如预期的那样，这种纳米药物不仅在两种血栓模型中实现了更有效的血栓溶解，而且在黑尾模型中通过治疗可视化延迟了血栓形成的进展。这种合理的治疗原则为血栓性疾病的综合治疗提供了广阔的平台。
Thrombotic diseases cause significant risks of disability and death worldwide. However, conventional thrombolytic drugs have short half-lives, poor targeting capabilities, limited therapeutic effects, and narrow therapeutic windows. Moreover, most basic studies focus only on thrombolytic efficiency and ignore the inflammatory factors that promote thrombosis progression, such as reactive oxygen species (ROS)-mediated oxidative stress. Therefore, to achieve comprehensive and effective thrombolytic management, both targeted thrombolytic therapy and the elimination of inflammatory factors must be achieved. In this study, we developed a platelet membrane (PM)-functionalized hollow mesoporous Prussian blue nanomedicine (HMPB-rtPA@PM), which was innovatively coassembled from two FDA-approved drugs (Prussian blue (PB) and alteplase (rtPA)) and showed marked advantages in both thrombi targeting and photothermal/pharmacological synergistic fibrinolysis. Moreover, HMPB-rtPA@PM exhibited the potential to inhibit platelet aggregation and regulate the inflammatory microenvironment by scavenging ROS. As expected, this nanomedicine not only achieved more efficient thrombolysis in both thrombus models but also delayed thrombosis progression through therapeutic visualization in the black tail model. Such rational therapeutic principle provides a broad platform for the comprehensive management of thrombotic diseases.