Drug Uptake Enhancement Using Sonodynamic Effects at 4 MHz—A Potential Application for Micro-Ultrasonic-Transducers

Abstract

Sonodynamic therapy is a cancer treatment method that uses macro scale ultrasound devices to enhance the cytotoxic efficacy of anticancer drugs, such as doxorubicin [1]. In this paper, unconventional, miniature ultrasound transducers (5 mm x 5 mm x 0.5 mm) were used to create a tone-burst ultrasound (4 MHz, 32 Watt/cm(2), 20% duty cycle, 50 ms burst period). It was found that the transducer significantly (p < 0.01) enhanced the immediate cells lysis when combining with doxorubicin (20 microM) in human prostate cancer cells (PC3). With a 30-s ultrasound exposure, the immediate cell lysis and long-term cytotoxicity were enhanced by 70% and 83%, respectively, compared to controls. We have demonstrated that ultrasound in combination with doxorubicin could strongly inhibit tumour cell proliferation in vitro at lower doses of the drug. This work is a first step towards a microelectromechanical system (MEMS)-based, implantable micro-ultrasonic transducers (MUTs) that could be used in sonodynamic therapy.