Direct Evidence of Multibubble Sonoluminescence Using Therapeutic Ultrasound and Microbubbles

Abstract

The intense conditions generated in the core of a collapsing bubble have been the subject of intense scrutiny from fields as diverse as marine biology and nuclear fusion. In particular, the phenomenon of sonoluminescence, whereby a collapsing bubble emits light, has received significant attention. Sonoluminescence has been associated predominantly with millimeter-sized bubbles excited at low frequencies and under conditions far removed from those associated with the use of ultrasound in medicine. In this study, however, we demonstrate that sonoluminescence is produced under medically relevant exposure conditions by microbubbles commonly used as contrast agents for ultrasound imaging. This provides a mechanistic explanation for the somewhat controversial reports of "sonodynamic" therapy, in which light-sensitive drugs have been shown to be activated by ultrasound-induced cavitation. To illustrate this, we demonstrate the activation of a photodynamic therapy agent using microbubbles and ultrasound. Since ultrasound can be accurately focused at large tissue depths, this opens up the potential for generating light at locations that cannot be reached by external sources. This could be exploited both for diagnostic and therapeutic applications, significantly increasing the range of applications that are currently restricted by the limited penetration of light in the tissue.

Zinc Oxide Nanocrystals and High-Energy Shock Waves: A New Synergy for the Treatment of Cancer Cells

“…The production of light flash upon inertial acoustic cavitation is actually a debated issue. Some authors proposed the possibility of the organic sonosensitizer activation through sonoluminescence (Ninomiya et al, 2014;Brazzale et al, 2016;Beguin et al, 2019). In this case, an eventual light excitation of ZnO NCs has, as a result, the ROS overproduction with consequent cell death (Ancona et al, 2018).…”

<p>Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles</p>

“…It is believed that the acoustic energy and sonoluminescence derived from ultrasonic cavitation is responsible for the excitation of the ZnPc, resulting in the formation of singlet oxygen when the energy is released on its return to the ground state. 71 The irradiation of Rose Bengal microbubbles, 72 indocyanine green microbubbles 73 and metalloporphyrins nanoparticles 16 for at least 30 s with 1 MHz ultrasound, also resulted in the production of singlet oxygen. The generation of singlet oxygen resulting from irradiation with LFU has only been described recently, by the irradiation of MnWOx bimetallic oxide nanoparticles with a 40 kHz ultrasound.…”

“…We hypothesize that the DSPE-PEG micelle, which composition is very similar to that of microbubbles reported in the literature, 74 , 75 could trap gas in its hydrophobic nucleus when subjected to LFU sonication, hence assisting sonoluminescence and 1 O 2 production. 71 There is no consensus on the precise mechanisms of generation of ROS assisted by cavitation microbubbles 71 although the production of singlet oxygen has been reported when some nanostructured systems such as microbubbles 71 and inorganic nanoparticles 76 were irradiated with 1 MHz ultrasound for at least 2 min. Therefore, further investigation is needed to evaluate the potential of blank DSPE-PEG micelles herein developed as nanobubbles for SDT.…”

Nanostructured TiO2 cavitation agents for dual-modal sonophotocatalysis with pulsed ultrasound

“…To amplify the sonochemical effects of cavitation, photosensitizers such as photosensitive semiconductors [5] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , graphene [18] , [23] , [24] , or polymers [25] , [26] have been used to promote radical species generation. Sonoluminescence from cavitation events in the fluid interacts with nearby photosensitizers to generate reactive oxygen species (ROS) [10] , [27] , [28] .…”