bc9b00653_si_001.pdf (1.18 MB)
Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity
journal contribution
posted on 2019-12-04, 15:45 authored by Ling Ma, Yinjie Wang, Shengmin Zhang, Xuechen Qian, Nianyu Xue, Zhenqi Jiang, Ozioma Udochukwu Akakuru, Juan Li, Youfeng Xu, Aiguo WuSonothrombolysis 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.