Ultrasound Therapy

We have been working on several projects involving the use of focused ultrasound to produce therapeutic effects. Projects include the use of ultrasound stimulated microbubbles in tumors to elicit an enhanced response to hyperthermia [1,2,3]. We have been collaborating with various laboratories in the Beckman Institute for Advanced Science and Technology to develop mechanophores that can produce either light or reactive oxidative species via ultrasound activation [4,5]. This would allow therapy to be delivered via ultrasound and injected nanophores. Figure 1 shows a figure depicting the emission of light from mechanophores exposed to focused ultrasound.

Figure 1. Mechanoluminescent behavior of dioxetane-functionalized PDMS: (A) Plot of the generated blue-light intensity versus time (a.u., arbitrary units); and (B) optical images showing the intensity versus HIFU irradiation time. The intensity plot is based on light generated in the focal spot (∼2.25 mm, 550 kHz). Green- and red-colored points in the plot indicate the start and end points of sonication, respectively. (Scale bar: 5.0 mm.)

References:

[1] G. Ghoshal, S. A. Swat, M. L. Oelze, “Enhancing cell kill from hyperthermia through pre-sensitizing with ultrasound-stimulated microbubbles,” Journal Acoustical Society of America, Express Letters, 138: EL493-EL497 , 2015.

[2] D. Sharma, A. Giles, A. Hashim J. Yip, Y. Ji, N.N.A. Do, W.T. Tran; G. Farhat, G.J. Czarnota, M.L Oelze; J. Sebastiani, “Ultrasound Microbubble Potentiated Enhancement of Hyperthermia-Effect in Tumours,” PLOS ONE, 14.12, 2019.

[3] D. Sharma, H. Cartar, N. Law, A. Giles, G. Farhat, M.L Oelze, G.J. Czarnota “Optimization of Microbubble Enhancement of Hyperthermia for Cancer Therapy in an in vivo Breast Tumour Model”, PLOS ONE, 15(8), e0237372, 2020.

[4] G. Kim, V.M. Lau, A.J. Halmes, M.L. Oelze, J.S. Moore, K.C. Li, “High-Intensity Focused Ultrasound-Induced Activation of Mechanochromism in Network Elastomers,” Proceedings of the National Academy of Sciences, 116(21): 10214-10222, 2019.

[5] G. Kim, Q. Wu, J.L. Chu, E.J. Smith, M.L. Oelze, K.C. Li, J.S. Moore, “Ultrasound controlled mechanophore activation in hydrogels for cancer therapy,” Proceedings of the National Academy of Sciences, 119:1-7, 2022.