RT Journal Article
SR Electronic
T1 Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 779124
DO 10.1101/779124
A1 David R. Mittelstein
A1 Jian Ye
A1 Erika F. Schibber
A1 Ankita Roychoudhury
A1 Leyre Troyas Martinez
A1 M. Houman Fekrazad
A1 Michael Ortiz
A1 Peter P. Lee
A1 Mikhail G. Shapiro
A1 Morteza Gharib
YR 2019
UL http://biorxiv.org/content/early/2019/10/01/779124.abstract
AB 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.