Ultrasound‐Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis
Ultrasound‐Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis
复制标题
超声响应纳米肽体可实现同步空间成像并抑制深静脉血栓形成中的凝块生长
DOI：
10.1002/adhm.202100520
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发表时间：
2021
影响因子：
10
通讯作者：
Medina, Scott H.
中科院分区：
文献类型：
--
作者：
Sloand, Janna N.;Rokni, Eric;Watson, Connor T.;Miller, Michael A.;Manning, Keefe B.;Simon, Julianna C.;Medina, Scott H.
深静脉血栓形成(DVT)是一种危及生命的血液凝结状态，如果未被发现，可能会导致致命的肺血栓。其临床管理的关键是快速检测、监测和治疗血栓形成的能力。然而，目前的诊断成像设备缺乏所需的分辨率来精确定位血管闭塞并实现实时血块监测。在这里，我们合理地设计了纤维蛋白原模拟荧光肽纳米乳剂，或纳米微球(NPep)，允许血栓的对比增强超声成像和同步抑制血栓生长。NPep的治疗二重性是通过它们与凝血过程中激活的血小板上过度表达的整合素的内在结合来传递的。与血小板结合的纳米乳剂可以蒸发并在外加声场中振荡，以实现对血栓的对比增强多普勒超声检测。同时，与血小板结合的纳米乳剂竞争性地抑制第二次血小板-纤维蛋白原结合，以破坏进一步的凝块生长。这一同步治疗平台的持续发展可能会为DVT和其他血管疾病的影像引导、非侵入性干预带来新的机会。
Deep vein thrombosis (DVT) is a life‐threatening blood clotting condition that, if undetected, can cause deadly pulmonary embolisms. Critical to its clinical management is the ability to rapidly detect, monitor, and treat thrombosis. However, current diagnostic imaging modalities lack the resolution required to precisely localize vessel occlusions and enable clot monitoring in real time. Here, we rationally design fibrinogen‐mimicking fluoropeptide nanoemulsions, or nanopeptisomes (NPeps), that allow contrast‐enhanced ultrasound imaging of thrombi and synchronous inhibition of clot growth. The theranostic duality of NPeps is imparted via their intrinsic binding to integrins overexpressed on platelets activated during coagulation. The platelet‐bound nanoemulsions can be vaporized and oscillate in an applied acoustic field to enable contrast‐enhanced Doppler ultrasound detection of thrombi. Concurrently, nanoemulsions bound to platelets competitively inhibit secondary platelet–fibrinogen binding to disrupt further clot growth. Continued development of this synchronous theranostic platform may open new opportunities for image‐guided, non‐invasive, interventions for DVT and other vascular diseases.