Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity.,Bioconjugate Chemistry

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Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2019-12-04 , DOI: 10.1021/acs.bioconjchem.9b00653
Ling Ma ₁ , Yinjie Wang _{2,

3} , Shengmin Zhang ₁ , Xuechen Qian _{1,

4} , Nianyu Xue ₁ , Zhenqi Jiang _{2,

3} , Ozioma Udochukwu Akakuru _{2,

3} , Juan Li ₂ , Youfeng Xu ₁ , Aiguo Wu ₂

Affiliation

Sonothrombolysis with microbubbles can enhance the dissolution of thrombus through the cavitation effect of microbubbles under ultrasound irradiation. However, the detailed mechanism of thrombolysis with microscaled or nanoscaled bubbles is still not so clear. This study compared the thrombolytic capacity of cRGD-targeted or nontargeted bubbles with different particle sizes combined with urokinase (UK). The size of the microscaled bubbles (Mbs or Mbs-cRGD) was mostly approximately 3 μm, while the nanoscaled bubbles (Nbs or Nbs-cRGD) were mainly around 220 nm. In vitro testing was performed on an extracorporeal circulation device that mimics human vascular thromboembolism. The rabbit clots in Mbs with UK groups showed peripheral worm-like dissolution, while the clots in Nbs with UK groups showed internal fissure-like collapse. In addition, the thrombolysis rate of Nbs-cRGD with the UK group was the highest. Furthermore, the scanning electron microscopic images showed that the fibrin network was the most severely damaged by the Nbs-cRGD, and most of the fibrin strands were dissolved. Especially, the Nbs-cRGD can penetrate much deeper than Mbs-cRGD into the thrombus and loosen the fibrin network. Taken together, benefiting from the specific identification and deep penetration to thrombus, our developed novel targeted Nbs may have broad application prospects in the clinic.

中文翻译：

有针对性的纳米气泡的深层渗透增强了对溶栓能力的空化作用。

具有微泡的声波溶栓可通过在超声照射下微泡的空化作用来增强血栓的溶解。但是，用微尺度或纳米尺度的气泡进行溶栓的详细机制仍不清楚。这项研究比较了不同粒径的cRGD靶向或非靶向气泡与尿激酶（UK）的溶栓能力。微米级气泡（Mbs或Mbs-cRGD）的大小大部分约为3μm，而纳米级气泡（Nbs或Nbs-cRGD）的大小主要约为220 nm。在模拟人血管血栓栓塞的体外循环设备上进行了体外测试。UK组的Mbs中的兔血块显示出外周蠕虫样溶解，而UK组的Nbs中的兔血块显示出内部裂缝样塌陷。此外，英国组的Nbs-cRGD溶栓率最高。此外，扫描电子显微镜图像显示，Nbs-cRGD对血纤蛋白网络的破坏最严重，并且大部分血纤蛋白链都溶解了。特别是，Nbs-cRGD可以比Mbs-cRGD更深地渗透到血栓中，并使纤维蛋白网络松弛。综合起来，得益于对血栓的特异性识别和深入渗透，我们开发的新型靶向Nb可能在临床上具有广阔的应用前景。Nbs-cRGD可以比Mbs-cRGD更深地渗透到血栓中，并释放纤维蛋白网络。综合起来，得益于对血栓的特异性识别和深入渗透，我们开发的新型靶向Nb可能在临床上具有广阔的应用前景。Nbs-cRGD可以比Mbs-cRGD更深地渗透到血栓中，并释放纤维蛋白网络。综合起来，得益于对血栓的特异性识别和深入渗透，我们开发的新型靶向Nb可能在临床上具有广阔的应用前景。

更新日期：2019-12-04

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