Controlled induction of mechanical bioeffects with pulsed ultrasound and chemical agents

Abstract

We aim to develop a novel low-invasive and effective treatment method of pancreatic tumor with synergistic effects of ultrasound and locally injected chemical agents such as anti-tumor drugs. In the treatment, controlling the spatial and temporal distribution of the agents by mechanical effects of ultrasound (cavitation) is a key process. To apply the mechanical effects to pancreases, a deep-seated organ, sensitizers for reducing the required acoustic intensity are essential. As preliminary experiments, we evaluated a formulation of superheated perfluorocarbon droplet, phase change nano droplet (PCND) as such a sensitizer. Effects on destruction of tissue structures were investigated ex vivo. It was found that ultrasound pulses with intensity higher than 2.2 kW/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> was enough to induce mechanical effects of ultrasound in chicken breast tissues in the presence of PCND while no damages were observed in the absence of PCND. Increasing pulse intensity or PCND concentration increased destructed volume. It was found that pulse duration should be longer than 100 cycles and increasing duration more than 300 cycles does not increase the destructed volume significantly. Results obtained suggested that PCND works as a sensitizer for inducing mechanical effects in tissues.