Influence Of Medium Physicochemical Properties On Acoustic Cavitation For Sonodynamic Therapy

Photodynamic therapy (PDT) is an established treatment for non-melanoma skin cancer, however, its efficacy in nodular and pigmented lesions is hindered by limited light penetration depth. To overcome this, sonodynamic therapy (SDT) has emerged as a promising alternative, combining a sensitizer molecule, low-intensity ultrasound and molecular oxygen to generate reactive oxygen species (ROS) and induce cell death. The efficiency of SDT is closely related to acoustic cavitation phenomena, whose dynamics are modulated by the physicochemical properties of the environment. This study aims to monitor and characterize acoustic cavitation in biologically relevant media to elucidate how physicochemical factors influence cavitation activity and ROS generation.  Acoustic cavitation activity was assessed using complementary indirect and direct approaches. Indirect monitoring was performed by potassium iodide (KI) dosimetry (0.2 M), in which cavitation-induced hydroxyl radicals (•OH) oxidize iodide ions (I^-) to form triiodide (I₃⁻). KI solutions prepared in ultrapure water, phosphate-buffered saline (PBS), dimethyl sulfoxide (DMSO), 1% Triton X-100, and 10% fetal bovine serum (FBS) were irradiated with ultrasound (1 MHz, 50% duty cycle, 100 Hz, and 1.5 W/cm²) in a custom setup using degassed water as the coupling medium. I₃^- was quantified by UV-Vis spectroscopy at 351 nm. The I₃^- formation rate constants (min⁻¹) were: k_water = (7.0 ± 0.1)x10^-7, k_PBS = (6.9 ± 0.1)x10^-7, k_DMSO = -(3.9 ± 1.8)x10^-9, k_surfactant = (1.9 ± 0.2)x10^-6 and k_FBS = -(5.8 ± 1.3)x10^-9, demonstrating that cavitation-induced I₃^- formation is highly dependent on the solvent physicochemical properties. Direct cavitation monitoring was performed using a calibrated needle hydrophone coupled to a digital oscilloscope to acquire real-time acoustic emissions from irradiated media. The setup was optimized to improve signal-to-noise ratio, and signals were analyzed using Fast Fourier Transform (FFT) to identify spectral features associated with cavitation regimes. Preliminary results in ultrapure and tap water showed distinct acoustic signatures, demonstrating the system’s capability to differentiate cavitation behavior across media. This study provides a basis for understanding acoustic cavitation behavior in biologically relevant media, offering insights relevant to the optimization of sonodynamic therapy for potential clinical applications study.