Combinations with Sonodynamic Therapy

Abstract

Like photodynamic therapy, sonodynamic therapy is based on ultrasonic activation of a sonodynamic therapy sensitizer to kill disease cells by production of reactive oxygen species in excess of what can be handled by cellular redox homeostasis biochemical pathways. As an evolution of photodynamic therapy, sonodynamic therapy introduces a new set of advantages over photodynamic therapy, top amongst which are an unlimited tissue penetration depth and a set of sonodynamic sensitizers well within that of photodynamic therapy. The two technologies are therefore conceptually quite easily combined by simultaneous application of light and ultrasound. Applications of the combination against cancer and bacterial pathogens are increasing. For example, the combination is proving to be exceptionally suitable for antibacterial and anticancer applications of bone disease such as the various osteomyelitis, osteosarcoma, and periodontitis presentations, where the photodynamic therapy treats mainly the superficial topical lesions and the sonodynamic therapy treats the deeper lying disease. Periodontal applications have taken a big fraction of the oral hygiene applications. Mechanistic studies are elucidating the reactive oxygen species generation, sonoporation-mediated photosensitizer trans-membrane transport, energy transfer processes, and cellular organelle targets. Sonodynamic therapy is most widely studied as an anti-cancer, antimicrobial, as well as combination with antimicrobial, anticancer, and chemotherapy, although triple-therapy combinations involving sonodynamic therapy are starting to show up in the literature. The technology has generated a series of patents on applications and devices, indicating that it is transitioning to the clinic, with an increasing number of case studies.