Optimizing sonodynamic therapy: a kinetic study of ROS generation via sonolysis

Reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals, are the primary cytotoxic agents responsible for the therapeutic efficacy of sonodynamic therapy (SDT). Their production is believed to be driven by acoustic cavitation, a physical phenomenon where ultrasound waves induce the formation, growth, and violent collapse of microbubbles in an aqueous medium. This collapse generates extreme temperatures and pressures, leading to the sonolysis of water and the formation of highly reactive radicals. Despite the critical role of these radicals, the specific physical and chemical conditions that optimize their generation are not yet fully understood. This study investigates the fundamental mechanisms of sonolysis for ROS production and identifies practical strategies to enhance these sonochemical processes. In order to do that, potassium iodide (KI) was utilized as a standard cavitation dosimeter. By measuring the formation of triiodide, which is a product of the reaction between KI and hydroxyl radicals, the study quantified the amount of cavitation generated using degassed versus non-degassed Milli-Q water as the coupling medium, with triiodide formation being monitored over time using spectrometric analysis. To further characterize the underlying kinetics, a mathematical model based on rate equations was developed and validated against the experimental measurements of triiodide formation. The experimental results demonstrate that degassed conditions significantly enhance cavitation yield, thereby highlighting the critical importance of a gas-free coupling medium to deliver acoustic energy and initiate cavitation efficiently. The kinetic analysis, based on the derived rate equations, revealed a first-order relationship between triiodide formation and sonication time, providing a good first approximation to predict and describe sonochemical kinetics. Collectively, these findings are important for advancing the fundamental understanding of sonochemical ROS generation and for developing practical strategies to optimize ultrasound parameters and, consequently, enhance the clinical efficacy of SDT.