Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound
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 (I_(SPTA) < 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.
© 2020 Published under license by AIP Publishing. Submitted: 22 September 2019; Accepted: 2 December 2019; Published Online: 7 January 2020. The authors thank Sangjin Yoo, Di Wu, Avinoam Bar-Zion, Dan Piraner, and Mohamad Abedi for helpful discussion. The authors also 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. The authors also thank Michael R. Bailey for his assistance in designing the pipet bulb pressure chambers and Maayan Harel (www.maayanillustration.com) 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. A.R. and L.T.M. were supported by Caltech Summer Undergraduate Research Fellowships. The authors declare no competing financial interest.
Published - 1.5128627.pdf
Submitted - 779124.full.pdf
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Supplemental Material - oncotripsy_in_vitro_supplemental_drm_v10.pdf
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