Funded Projects

Sonodynamic therapy (SDT) is an emerging approach for eradication of tumors, which involves a combination of low-intensity ultrasound and specialized drugs known as sonosensitizers. In response to sonoluminescence, generated by cavitation of the surrounding liquid medium upon ultrasound activation, sonosensitizers produce cytotoxic reactive oxygen species (ROS) that can effectively destroy cancer cells. The deep penetration of ultrasound enables treatment of deep-seated tumors. Despite its breakthrough potential, SDT is still at a very early stage of development and the mechanisms of ROS generation by ultrasound are poorly understood. Furthermore, production of ROS within large tumors is ineffective because of the hypoxic environment. This proposal will address the current limitations of SDT and support the development of efficient nanocarrier based approaches. In order to move our multidisciplinary team into this new area, in which we have not previously published work, we propose the following specific aims: Specific Aim 1: Characterization of the mechanisms of SDT via multi-scale modeling and characterization of ROS production in biological microenvironment. We will study the formation of shock waves within collapsing gas bubbles in different biological media to quantify the excitation efficiency of sonosensitizers, using both computational and experimental approaches. We hypothesize that ROS production levels may vary depending on protein concentration, viscosity, pH, and other factors in the tumor environment. Specific Aim 2: Development of nanocariers to deliver sonosensitizers and oxygen to the tumors to affect SDT. We will produce nanoemulsions containing both sonosensitizers and oxygen-releasing agents to affect efficient SDT in hypoxic tumor environments. Specific Aim 3: Validation of a novel SDT platform in cell culture models. We will validate and optimize SDT to induce apoptosis in cultured cells, comparing it to conventional photodynamic therapy.