Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots.

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots.
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DOI:
10.1038/s41378-020-00228-9
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发表时间:
2021
影响因子:
7.9
通讯作者:
Jiang X
Jiang X
中科院分区:
工程技术1区
文献类型:
--
作者:
Goel L;Wu H;Zhang B;Kim J;Dayton PA;Xu Z;Jiang X

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当前微泡(MB)和组织纤溶酶原激活剂(tPA)介导的超声溶栓技术的一个主要挑战是有效地治疗收缩的血凝块,这是由于收缩的血凝块的高密度和低孔隙率。纳米液滴(ND)由于其小的尺寸和渗透到缩回的凝块中以增强药物递送的能力而具有增强缩回的凝块溶解的潜力。这是第一次,我们证明了亚兆赫,前视血管内(FVI)换能器可用于ND介导的超声溶栓,在体外。在这项研究中,我们确定了最小峰值负压诱导空化与低沸点相变纳米液滴和凝块溶解。然后,我们将纳米液滴介导的超声溶栓与MB和tPA介导的技术进行了比较。对照组、tPA单药组、tPA + US组、MB + US组、MB + tPA + US组、ND + US组和ND + tPA + US组的凝块溶解(收缩凝块质量减少百分比)分别为9 ± 8%、9 ± 5%、16 ± 5%、14 ± 9%、17 ± 9%、30 ± 8%和40 ± 9%。在回缩的血凝块中,与传统的MB和tPA介导的超声溶栓技术相比,ND和tPA介导的超声溶栓组合能够显著增强回缩的血凝块溶解。将nanodroplet与tPA介导的超声溶栓相结合可能为安全治疗回缩血栓提供可行的策略。
One major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.
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