Theoretical study of the conditions for acoustic nucleation and cavitation in biological tissue for its application in sono-photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a therapeutic modality that combines light, a light-activated drug, and the molecular oxygen of the medium to disrupt cells. Due to the low penetration of light in biological tissue and its absorption by pigmented cells, such as melanoma, the effective application of PDT is usually limited to superficial and non-pigmented lesions. The utilization of ultrasound-based therapies, such as Sonodynamic therapy (SDT) and Sono-photodynamic Therapy (SPDT), poses a possible solution to overcome these limitations. Besides the greater penetration of acoustic waves in the tissue, the propagation of ultrasonic waves can form gas/vapor bubbles in the medium and cause its subsequent oscillation and implosion, known as acoustic nucleation and cavitation. The implosion of oscillating bubbles can generate sonomechanical and sonochemical effects, such as the production of reactive oxygen species (ROS) by pyrolysis and sonoluminescence, leading to tumor death. This study aims to obtain, in a first approximation, the profile of light and ultrasound penetration in skin and melanoma cells, as well as the increase in temperature generated by the implosion of cavitated bubbles. For this purpose, the Monte Carlo eXtreme (MCX) and k-wave toolbox for MATLAB were used to obtain the beam profile of light and ultrasound, respectively, in skin and melanoma. For obtaining the inertial cavitation threshold and the peak of temperature due to the bubble's implosion, the Keller-Miksis (KM) equation was solved in the software Wolfram Mathematica. While the results were obtained from simplified models, they corroborate the greater penetration of ultrasound (US) in skin and melanoma when compared to light. While light at a wavelength (λ) equal to 630 nm reaches less than 3 mm within the tissue, US waves at the frequency of 1 MHz and acoustic pressure equal to 0.32 MPa can penetrate 15 mm, and the acoustic intensity is smoothly reduced in melanoma. Furthermore, the implosion of the cavitated bubbles can generate a local increase in temperature up to 1000 K, which can be responsible for the generation of ROS. Despite the need for more refined models to describe these phenomena with greater precision, they demonstrate that the utilization of SDT and SPDT can be a good approach for the effective and noninvasive treatment of melanoma.