Sonodynamic therapy for focal cancer treatment

Abstract

Current standard cancer treatments, such as radiation therapy, chemotherapy, and surgery, have limitations due to their systemic toxicities and invasive nature. Developing a new modality capable of controlling reactive oxygen species (ROS) generation in a spatiotemporal manner can circumvent this problem. For instance, photodynamic therapy (PDT) has attracted attention owing to its capability to generate ROS in a spatially controlled area and has shown clinical success in local cancer treatment. However, its noninvasiveness is limited to shallow areas like skin due to its low penetration depth. This talk presents a noble approach called sonodynamic therapy (SDT) that use high-intensity focused ultrasound (HIFU) and mechanophores to spatiotemporally control the generation of ROS. In SDT, HIFU delivers spatiotemporally controlled ultrasonic energy (i.e., radiation forces) to azo mechanophores (i.e., force-responsive moieties) embedded into polyethylene glycol (PEG) hydrogel. Upon mechanical irradiation with HIFU, azo mechanophores yield free radicals (FRs) that converts to ROS. Using two sets of mouse cancer models, breast cancer (E0771) and melanoma (B16F10), cell proliferation is monitored for 72 hours with 24-hour intervals. We confirmed the inhibition of growth and decrease in viability in response to the release of ROS by mechanophore activation, which is comparable to lethal doses of H2O2. Sonication of control gels also shows no cytotoxicity, demonstrating the biocompatibility of azo mechanophores. This study demonstrates the potential of the proposed SDT method as a new ROS delivery platform that overcomes the issues in current anticancer tools. Furthermore, this preliminary result opens a pathway toward biomedical applications of HIFU, such as metal ion detection, other drug leases, optogenetics, etc.