Low-Intensity Focused Ultrasound-Responsive Phase-Transitional Nanoparticles for Thrombolysis without Vascular Damage: A Synergistic Nonpharmaceutical Strategy
Low-Intensity Focused Ultrasound-Responsive Phase-Transitional Nanoparticles for Thrombolysis without Vascular Damage: A Synergistic Nonpharmaceutical Strategy
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低强度聚焦超声响应相变纳米颗粒用于溶栓而不损伤血管：一种协同非药物策略
DOI：
10.1021/acsnano.8b09277
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发表时间：
2019
期刊：
影响因子：
17.1
通讯作者：
Guo Dajing
中科院分区：
文献类型：
--
作者：
Zhong Yixin;Zhang Yu;Xu Jie;Zhou Jun;Liu Jia;Ye Man;Zhang Liang;Qiao Bin;Wang Zhi-gang;Ran Hai-tao;Guo Dajing
多模式分子成像已显示出作为血栓检测的补充方法的前景。然而，同时无创检测和溶解血栓的心血管疾病仍然具有挑战性。本文中，制备了基于全氟己烷（PFH）的生物相容性纳米结构，即制备的Fe 3 O 4-聚（乳酸-共-乙醇酸）-PFH-CREKA纳米颗粒（NPs），其结合了联合收割机的相变（PT）溶栓能力和有利于多模态成像的性质。这种开发良好的PT剂有效地响应于低强度聚焦超声（LIFU），通过触发液体PFH的汽化来实现血栓溶解。CREKA肽的存在，结合到血栓的纤维蛋白，允许靶向成像和有效的血栓溶解。然后，我们发现，与使用非相变剂的溶栓相比，PT溶栓可以产生血栓负荷的稳健降低，而与LIFU的声功率密度无关。特别是，在溶解过程中LIFU反应性PT的能量降低保证了PT溶栓的上级安全性。在静脉注射NPs后，我们证明了这种裂解过程可以用超声和光声成像在体内监测，以评估其疗效。因此，这种非药物策略偏离常规方法，并揭示了PT溶栓作为目前溶栓治疗的有效和非侵入性替代方法的潜在用途。
Multimodal molecular imaging has shown promise as a complementary approach to thrombus detection. However, the simultaneous noninvasive detection and lysis of thrombi for cardiovascular diseases remain challenging. Herein, a perfluorohexane (PFH)-based biocompatible nanostructure was fabricated, namely, as-prepared Fe3O4-poly(lactic-co-glycolic acid)-PFH-CREKA nanoparticles (NPs), which combine phase transition (PT) thrombolysis capabilities with properties conducive to multimodal imaging. This well-developed PT agent responded effectively to low-intensity focused ultrasound (LIFU) by triggering the vaporization of liquid PFH to achieve thrombolysis. The presence of the CREKA peptide, which binds to the fibrin of the thrombus, allows targeted imaging and efficacious thrombolysis. Then, we found that, compared with thrombolysis using a non-phase-transition agent, PT thrombolysis can produce a robust decrease in the thrombus burden regardless of the acoustic power density of LIFU. In particular, the reduced energy for LIFU-responsive PT during the lysis process guarantees the superior safety of PT thrombolysis. After injecting the NPs intravenously, we demonstrated that this lysis process can be monitored with ultrasound and photoacoustic imagingin vivoto evaluate its efficacy. Therefore, this nonpharmaceutical strategy departs from routine methods and reveals the potential use of PT thrombolysis as an effective and noninvasive alternative to current thrombolytic therapy.