Although nanotechnology has shown great promise for treating multiple vascular diseases in recent years, simultaneous noninvasive detection and efficient dissolution of deep venous thrombosis (DVT) still remains challenging. In particular, long blockage areas and large thrombus thicknesses in DVT cause enormous difficulties for site-specific deep-seated thrombus theranostics. Therefore, based on the unique components of DVT, the novel concept of a thrombin-responsive full-thickness infiltration nonpharmaceutical nanoplatform for DVT theranostics is proposed here. The penetration depth is innovatively enhanced with efficient targeting and accumulation in the whole thrombi. Herein, we report a thrombin-responsive phase-transition liposome incorporating a liquid perfluoropentane (PFP) core and modified with two binding peptides, activatable cell-penetrating peptide (ACPP) and fibrin-binding ligand (FTP), which contribute to efficient liposome targeting and accumulation within the thrombi. This targeted nanoplatform is constructed to dig out the thrombus with the assistance of low-intensity focused ultrasound (LIFU), performing the destructive function of an excavator via an acoustic droplet vaporization effect (acting as a “nanoexcavator” system), which can activate and vaporize into microbubbles to enhance LIFU efficacy. The resulting microbubbles enable real-time monitoring of the therapeutic process with ultrasound imaging and high performance photoacoustic imaging after loading DIR. This non-invasive nonpharmaceutical thrombolytic strategy is an improvement over existing clinical methods without systemic side effects.

中文翻译：

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凝血酶响应型工程纳米挖掘机，具有全厚度浸润能力，可用于无药物的深静脉血栓形成治疗学。

尽管近年来纳米技术已显示出治疗多种血管疾病的广阔前景，但同时进行无创检测和有效溶解深静脉血栓形成（DVT）仍然具有挑战性。尤其是，DVT中较长的阻塞区域和较大的血栓厚度给特定位置的深部血栓治疗学带来了巨大的困难。因此，基于DVT的独特成分，在此提出了针对DVT治疗学的凝血酶响应性全厚度浸润非药物纳米平台的新概念。通过有效地靶向和在整个血栓中蓄积，创新地提高了渗透深度。在此，我们报告了一种凝血酶响应相变脂质体，该脂质体掺入了液体全氟戊烷（PFP）核心并被两个结合肽修饰，可激活的细胞穿透肽（ACPP）和纤维蛋白结合配体（FTP），它们有助于脂质体的有效靶向和在血栓中的蓄积。该靶向纳米平台可在低强度聚焦超声（LIFU）的帮助下挖出血栓，从而发挥挖掘机的破坏功能通过声滴汽化作用（充当“纳米挖掘机”系统），可以激活并汽化成微气泡以增强LIFU功效。产生的微气泡可以在加载DIR后通过超声成像和高性能光声成像实时监测治疗过程。这种非侵入性的非药物溶栓策略是对现有临床方法的改进，没有系统性副作用。