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.

由于缩回凝块的高密度和低孔隙度，当前微泡（MB）和组织纤溶酶原激活物（tPA）介导的溶栓治疗技术的一大挑战是有效治疗缩回的血凝块。纳米滴（NDs）由于其较小的尺寸和渗透到收缩的血凝块中以增强药物递送的能力而具有增强收缩的血凝块裂解的潜力。首次，我们证明了亚兆赫兹，前瞻性血管内（FVI）换能器可用于ND介导的超声溶栓。在这项研究中，我们确定了低沸点相变纳米滴和凝块溶解引起空化的最小峰值负压。然后，我们比较了纳米液滴介导的超声溶栓与MB和tPA介导技术。对照的血块溶解度以收缩血块质量减少的百分比为9±8％，9±5％，16±5％，14±9％，17±9％，30±8％和40±9％组，单独的tPA，tPA + US，MB + US，MB + tPA + US，ND + US和ND + tPA + US组。与传统的MB和tPA介导的超声溶栓技术相比，在缩回的血凝块中，ND和tPA介导的超声溶栓治疗能够显着增强缩回的血凝块溶解。纳米滴与tPA介导的溶栓治疗相结合可能为安全治疗缩回的血栓提供可行的策略。与传统的MB和tPA介导的超声溶栓技术相比，ND和tPA介导的超声溶栓治疗相结合能够显着增强缩回的血块溶解。纳米滴与tPA介导的溶栓治疗相结合可能为安全治疗缩回的血栓提供可行的策略。与传统的MB和tPA介导的超声溶栓技术相比，ND和tPA介导的超声溶栓治疗相结合能够显着增强缩回的血块溶解。纳米滴与tPA介导的溶栓治疗相结合可能为安全治疗缩回的血栓提供可行的策略。