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. 2021 Jan 6:7:3.
doi: 10.1038/s41378-020-00228-9. eCollection 2021.

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Leela Goel  1   2 , Huaiyu Wu  1 , Bohua Zhang  1 , Jinwook Kim  2 , Paul A Dayton  2 , Zhen Xu  3 , Xiaoning Jiang  1
Affiliations

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Leela Goel et al. Microsyst Nanoeng. .

Abstract

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.

Keywords: Biosensors; Engineering; Nanoparticles.

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Conflict of interest statement

Competing interestsXiaoning Jiang has financial interest in Sonovascular, Inc. who licensed an intravascular sonothrombolysis technology from NC State. Paul Dayton is an inventor on several patents, describing the low-boiling point phase change nanodroplets described here, and is a co-founder of Triangle Biotechnology, Inc., which has licensed these patents. Zhen Xu has financial interest in HistoSonics.

Figures

Fig. 1
Fig. 1. Experimental setup.
Diagram of a forward-viewing intravascular transducer catheter assembly and b experimental flow model
Fig. 2
Fig. 2. Nanodroplet activation.
a Inertial and b stable cavitation doses for nanodroplet mediated (ND) sonothrombolysis with different peak negative pressures compared with a control group of phosphate buffered saline (PBS) with ultrasound. The ultrasound excitation parameters were 700kHz, 10ms pulse length, and 20 cycles. * indicates p < 0.05 compared with the control group (N = 3)
Fig. 3
Fig. 3. Retracted clot lysis results for different treatment conditions with a peak negative pressure of 0.9 MPa.
* indicates p < 0.05 compared with ND+US and † indicates p < 0.05 compared with ND+tPA+US. (N = 6)
See this image and copyright information in PMC

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