Optimizing ultrasound parameters for enhanced sonodynamic therapy: A physical approach to tumor treatment

Sonodynamic therapy (SDT) leverages the energy of ultrasound (US) waves to activate sonosensitizers such as IR-780, offering a localized and targeted approach to anticancer treatment. This study focuses on the physical parameters of ultrasound application, including frequency (1.505 MHz), intensity (0.63–1.66 W/cm²), and exposure duration (3 min), tailored for both two-dimensional (2-D) and three-dimensional (3-D) pancreatic cancer cell models. The high penetrative capacity of the US ensures precise energy delivery to tumor sites while limiting damage to surrounding healthy tissues. In 3-D spheroid cultures, SDT effectively reduced tumor volume and disrupted structural integrity, driven by mechanical stress and cavitation effects induced by ultrasonic energy. Optimized power settings and duty cycles were essential for enhancing therapeutic outcomes while avoiding thermal damage. The interplay between ultrasound-induced pressure variations and sonosensitizer activation facilitated the generation of reactive oxygen species(ROS), causing localized cytotoxic effects within the tumor microenvironment. These findings demonstrate the potential of ultrasound as a dual-purpose tool for therapy and drug delivery in oncology. By exploiting its non-invasive nature, deep tissue penetration, and high spatial selectivity, SDT provides a promising platform for addressing treatment-resistant tumors, particularly pancreatic cancer. Further refinement of ultrasonic parameters will support its translation into clinical practice.