A Comparison of Sonothrombolysis in Aged Clots between Low-Boiling-Point Phase-Change Nanodroplets and Microbubbles of the Same Composition

Kim, Jin-Wook; DeRuiter, Ryan; Goel, Leela; Xu, Zhen; Jiang, Xiaoning; Dayton, Paul A.

doi:10.1016/j.ultrasmedbio.2020.07.008

Cited by 42 publications

(19 citation statements)

References 32 publications

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“…In addition, this was achieved using a relatively low PNP of 0.9 MPa (within the FDA safety limit mechanical index = 1.9) compared with higher PNP's of up to 15 MPa as used in other external sonothrombolysis techniques for retracted clots 18 . Previous studies utilizing nanodroplets using high intensity focused ultrasound with PNPs ranging from 2 to 8 MPa were conducted using fresh, unretracted clots, and resulted in percent mass decreases of 25-80% after 30 minutes of treatment 22,24,25 . In this study, we were able to achieve a percent mass decrease of 40% using only 0.9 MPa under similar conditions in retracted clots.…”

Section: Discussionmentioning

confidence: 99%

“…Given the small size of NDs (100-300 nm) compared with MBs (1-10 μm), NDs have the potential to penetrate into retracted clots with low porosity. Upon insonation, these droplets can then form microchannels within the clot and act to both mechanically break down the clot via cavitation effects and allow for greater diffusion of tPA and cavitation effects inside the clots 20,25 .…”

Section: Nanodroplet-mediated Sonothrombolysismentioning

confidence: 99%

“…Although initial studies are promising, it requires the PNPs of 3-5 MPa to activate the ND, which exceeds the safety limit for ultrasound imaging and causes concerns for clinical translation. Low-boiling point phase change NDs may overcome the limitations of current ND techniques by reducing the pressure necessary for ND activation and by extension clot lysis, thus allowing a lower PNP output necessary to treat retracted clots 22,25,26 . These low-boiling point phase change nanodroplets are designed to be stable at up to 37 ∘ C and have a vaporization threshold at~1 MPa 26 .…”

Section: Nanodroplet-mediated Sonothrombolysismentioning

confidence: 99%

“…Lipid-shelled, decafluorobutane (DFB) gas core nanodroplets were prepared as previously described 25,26 . In brief, lipid-shelled DFB MB were synthesized and condensed into liquid-core nanodroplets with an average size of 100-200 nm and concentration of 10 10 ND/ml.…”

Section: Treatment Condition Preparationmentioning

confidence: 99%

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Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Goel

Zhang

et al. 2021

Microsyst Nanoeng

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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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Section: Discussionmentioning

confidence: 99%

Section: Nanodroplet-mediated Sonothrombolysismentioning

confidence: 99%

Section: Nanodroplet-mediated Sonothrombolysismentioning

confidence: 99%

Section: Treatment Condition Preparationmentioning

confidence: 99%

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Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Goel

Zhang

et al. 2021

Microsyst Nanoeng

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“…The resulting bubble, which cavitates in the ultrasound field, likely facilitates tissue dispersion, with the additional advantage of enhanced penetration of tissue while in the liquid nanodroplet precursor stage ( Pajek et al 2014 ). A similar principal has been applied for medical acoustics in which cavitation has been shown to disrupt intravascular blood clots ( Kim et al 2020 ), as well as endothelial and epithelial barriers ( Chen et al 2013 ; Fix et al 2019 ). Depending on the duration of sonication, the degree of chromatin fragmentation in the presence of nanodroplets can be controlled ( Figs.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide cancer-specific chromatin accessibility patterns derived from archival processed xenograft tumors

et al. 2021

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Chromatin accessibility states that influence gene expression and other nuclear processes can be altered in disease. The constellation of transcription factors and chromatin regulatory complexes in cells results in characteristic patterns of chromatin accessibility. The study of these patterns in tissues has been limited because existing chromatin accessibility assays are ineffective for archival formalin-fixed, paraffin-embedded (FFPE) tissues. We have developed a method to efficiently extract intact chromatin from archival tissue via enhanced cavitation with a nanodroplet reagent consisting of a lipid shell with a liquid perfluorocarbon core. Inclusion of nanodroplets during the extraction of chromatin from FFPE tissues enhances the recovery of intact accessible and nucleosome-bound chromatin. We show that the addition of nanodroplets to the chromatin accessibility assay formaldehyde-assisted isolation of regulatory elements (FAIRE), does not affect the accessible chromatin signal. Applying the technique to FFPE human tumor xenografts, we identified tumor-relevant regions of accessible chromatin shared with those identified in primary tumors. Further, we deconvoluted non-tumor signal to identify cellular components of the tumor microenvironment. Incorporation of this method of enhanced cavitation into FAIRE offers the potential for extending chromatin accessibility to clinical diagnosis and personalized medicine, while also enabling the exploration of gene regulatory mechanisms in archival samples.

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Beyond silence: evolving ultrasound strategies in the battle against cardiovascular thrombotic challenges

Wang,

Jiang,

Jiang

et al. 2024

J Thromb Thrombolysis

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A Comparison of Sonothrombolysis in Aged Clots between Low-Boiling-Point Phase-Change Nanodroplets and Microbubbles of the Same Composition

Cited by 42 publications

References 32 publications

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Genome-wide cancer-specific chromatin accessibility patterns derived from archival processed xenograft tumors

Beyond silence: evolving ultrasound strategies in the battle against cardiovascular thrombotic challenges

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