Ultrasonic Activation of the Sonosensitizer Fimaporfin Enhances the Efficacy of Chemotherapy: An In Vitro Study on Rat Glioma Cells

Abstract

Activation of sonosensitizers via focused ultrasound, i.e., sonodynamic therapy, has been proposed as an alternative to light-activated photodynamic therapy for the treatment of a number of conditions from cancer to bacterial infections. The use of focused ultrasound allows treatment to sites buried deep within tissues, overcoming one of the main limitations of light-based modalities. Photochemical internalization is a technique that utilizes the photochemical properties of photodynamic therapy for the release of trapped endo-lysosomal macromolecules into the cell cytoplasm, greatly enhancing their efficacy. We have examined ultrasonic activation of disulfonated tetraphenyl chlorin (fimaporfin) together with the anti-cancer agent bleomycin, termed sonochemical internalization, as an alternative to light-activated photochemical internalization. Our results indicate that, compared to drug or focused ultrasound treatment alone, focused ultrasound activation of fimaporfin together with BLM significantly inhibits the viability of glioma monolayers and the treated cells’ ability to form clonogenic colonies.