Unseeded Cavitation with Confocal Ultrasound for the Potentiation of Doxorubicin

Abstract

Ultrasonic cavitation is of great interest in various biomedical applications. In cancer therapy, various ways to enhance chemotherapeutic agents has been explored. The present work emploies a two confocal transducers apparatus and a control loop with passive cavitation detector to generate cavitation in a controlled manner. Firstly, in vitro experiments show for stable cavitation the possibility to increase the efficacy of doxorubicin. Mechanistic studies suggest an indirect interaction between cavitation and the efficiency of DNA repair processes of the studied 4T1 tumor cells. Although this result was not observable in vivo, a safety study was conducted in vivo. Both the effect on healthy tissues and the potential metastatic spreading were assessed. Only slight damages were observed on healthy tissues. It was also shown a reduced metastatic spreading compared in mice which received ultrasound. This suggests the safety and the possibility to employ cavitation in vivo.