Although HIFU therapy is very low invasive method for tumor treatment, its time inefficiency and the absence of focus detecting mechanism of current systems limit the number of applicable cases. For an improved HIFU tumor treatment system, we propose to utilize a non-echogenic liquid nano droplet which turns into highly echogenic microbubbles upon non-therapeutic ultrasound pulses. Such a nano droplet would give echographic information on the focus of HIFU when exposed to the pulse and accelerate HIFU treatment by enhancing the ultrasonic energy deposition as microbubble As such a nanoparticle system, we developed a phase change nano droplet (PCND) which consists of superheated perfluorocarbon nano droplet coated with PEGylated phospholipids.
Microbubbles generation from PCND in tumor tissues was investigated by using mice, rats, and rabbits. It was found that 4 cycles of ultrasound pulses in the range of 3-8 MHz with negative peak pressure of about 3 MPa can generate microbubbles at tumor tissues in each animal 5 minutes after PCND was administered intravenously.
Significance of PCND to enhance ultrasonically induced therapeutic effects was also investigated. At frequency of 2 and 3 MHz, it was found that the presence of PCND (and generated microbubbbles) halved the intensity threshold for inducing thermal damage in murine tumor tissues. At frequency around 1 MHz, it was also found that the presence of PCND halved the threshold for inducing damage in murine tumor and the damage was induced both by thermal and cavitational effects of ultrasound.