Ultrasound can be focused into deep tissues with millimeter precision to perform noninvasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit nonselective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here, we describe an alternative low intensity (ISPTA < 5 W/cm2) pulsed ultrasound approach that leverages the distinct mechanical properties of neoplastic cells to achieve inherent cancer selectivity. We show that ultrasound applied at a frequency of 0.5–0.67 MHz and a pulse duration of >20 ms causes selective disruption of 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 nonselective high intensity ultrasound ablation.
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Selective ablation of cancer cells with low intensity pulsed ultrasound
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6 January 2020
Research Article|
January 07 2020
Selective ablation of cancer cells with low intensity pulsed ultrasound
David R. Mittelstein
;
David R. Mittelstein
1
Division of Engineering and Applied Sciences, California Institute of Technology
, Pasadena, California 91125, USA
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Jian Ye;
Jian Ye
2
Department of Immuno-Oncology, Beckman Research Institute, City of Hope
, Duarte, California 91010, USA
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Erika F. Schibber
;
Erika F. Schibber
1
Division of Engineering and Applied Sciences, California Institute of Technology
, Pasadena, California 91125, USA
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Ankita Roychoudhury;
Ankita Roychoudhury
1
Division of Engineering and Applied Sciences, California Institute of Technology
, Pasadena, California 91125, USA
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Leyre Troyas Martinez
;
Leyre Troyas Martinez
1
Division of Engineering and Applied Sciences, California Institute of Technology
, Pasadena, California 91125, USA
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M. Houman Fekrazad
;
M. Houman Fekrazad
2
Department of Immuno-Oncology, Beckman Research Institute, City of Hope
, Duarte, California 91010, USA
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Michael Ortiz
;
Michael Ortiz
1
Division of Engineering and Applied Sciences, California Institute of Technology
, Pasadena, California 91125, USA
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Peter P. Lee
;
Peter P. Lee
2
Department of Immuno-Oncology, Beckman Research Institute, City of Hope
, Duarte, California 91010, USA
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Mikhail G. Shapiro
;
Mikhail G. Shapiro
a)
3
Division of Chemistry and Chemical Engineering, California Institute of Technology
, Pasadena, California 91125, USA
a)Authors to whom correspondence should be addressed: mikhail@caltech.edu and mgharib@its.caltech.edu
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Morteza Gharib
Morteza Gharib
a)
1
Division of Engineering and Applied Sciences, California Institute of Technology
, Pasadena, California 91125, USA
a)Authors to whom correspondence should be addressed: mikhail@caltech.edu and mgharib@its.caltech.edu
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a)Authors to whom correspondence should be addressed: mikhail@caltech.edu and mgharib@its.caltech.edu
Appl. Phys. Lett. 116, 013701 (2020)
Article history
Received:
September 22 2019
Accepted:
December 02 2019
Citation
David R. Mittelstein, Jian Ye, Erika F. Schibber, Ankita Roychoudhury, Leyre Troyas Martinez, M. Houman Fekrazad, Michael Ortiz, Peter P. Lee, Mikhail G. Shapiro, Morteza Gharib; Selective ablation of cancer cells with low intensity pulsed ultrasound. Appl. Phys. Lett. 6 January 2020; 116 (1): 013701. https://doi.org/10.1063/1.5128627
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