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Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound

Mittelstein, David R. and Ye, Jian and Schibber, Erika F. and Roychoudhury, Ankita and Martinez, Leyre Troyas and Fekrazad, M. Houman and Ortiz, Michael and Lee, Peter P. and Shapiro, Mikhail G. and Gharib, Morteza (2019) Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound. . (Unpublished)

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Ultrasound can be focused into deep tissues with millimeter precision to perform non-invasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit non-selective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here we describe an alternative low intensity pulsed ultrasound approach that leverages the distinct mechanical properties of neoplastic cells to achieve inherent cancer selectivity. We show that when applied at a specific frequency and pulse duration, focused ultrasound selectively disrupts a panel of breast, colon, and leukemia cancer cell models in suspension without significantly damaging healthy immune or red blood cells. Mechanistic experiments reveal that the formation of acoustic standing waves and the emergence of cell-seeded cavitation lead to cytoskeletal disruption, expression of apoptotic markers, and cell death. The inherent selectivity of this low intensity pulsed ultrasound approach offers a potentially safer and thus more broadly applicable alternative to non-selective high intensity ultrasound ablation.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Mittelstein, David R.0000-0001-8747-0483
Ye, Jian0000-0002-7168-0117
Schibber, Erika F.0000-0002-6629-297X
Lee, Peter P.0000-0002-2660-4377
Shapiro, Mikhail G.0000-0002-0291-4215
Gharib, Morteza0000-0003-0754-4193
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. The authors thank Sangjin Yoo, Di Wu, Avinoam Bar-Zion, Dan Piraner, and Mohamad Abedi for helpful discussion. We thank Sangjin Yoo for guidance with ultrasound LIPUS bioeffects in neuromodulation, Dan Piraner for cell culture and fluorescent protein transfection, Hunter Davis for input on HFR imaging optics, and Di Wu for fluorescent cell tracking experiments. We thank Michael R. Bailey for his assistance in designing the pipet bulb pressure chambers. We thank Maayan Harel ( for the illustrations in this paper. Confocal microscopy experiments were performed at Caltech’s Beckman Imaging Facility. This project was supported by Amgen CBEA 2017, 2018 and the Caltech/ City of Hope collaborative grant 2019. AR and SLT were supported by Caltech Summer Undergraduate Research Fellowships. AUTHOR CONTRIBUTIONS: DRM, MO, MGS, MG conceived the study. DRM, JY, AR, SLT, MO, PL, MGS, MG designed, planned, and conducted the experiments in this paper. DRM and JY analyzed the data. All authors discussed the results. DRM, JY, and MGS wrote the manuscript with input from all the authors. All the authors have given their approval for the final version of the manuscript. MGS and MG supervised the research. The authors declare no competing financial interests.
Funding AgencyGrant Number
Caltech/City of Hope Biomedical InitiativeUNSPECIFIED
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Record Number:CaltechAUTHORS:20191002-094950438
Persistent URL:
Official Citation:Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound David Reza Mittelstein, Jian Ye, Erika F. Schibber, Ankita Roychoudhury, Sara Leyre Troyas, M Houman Fekrazad, Michael Ortiz, Peter P Lee, Mikhail G. Shapiro, Morteza Gharib bioRxiv 779124; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99007
Deposited By: George Porter
Deposited On:02 Oct 2019 17:26
Last Modified:03 Oct 2019 21:46

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