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Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound

By 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

Posted 01 Oct 2019
bioRxiv DOI: 10.1101/779124 (published DOI: 10.1063/1.5128627)

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.

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