Investigation of Focused Ultrasound Combined with Microbubbles to Enhance the Accumulation and Efficacy of Anticancer Nanodrug in Mouse Tumors

The main goal of drug delivery is to enhance the drug accumulation in tumor tissue in order to control the tumor growth, and to decrease drug concentration in other sites of the body to avoid side effect on normal tissues. Such treatment is so-called “targeted therapy.” High intensity focused ultrasound (HIFU) has been used for clinical therapy for years. Recently, it was found that the cavitation effect due to ultrasound sonication and ultrasound contrast agent was beneficial to local drug delivery.
In this study, we used s.c. colon carcinoma CT-26 mice tumor model and sonicated the tumors with focused ultrasound (frequency 1 MHz、1% duty cycle、pulse length 10ms、pulse repetition frequency 1Hz、pressure 1.2 MPa、total duration 120 seconds) after the injection of ultrasound contrast agent (SonoVue○R), and then inkected nanoparticles—commercial nanodrug Doxil○R (Ben Venue, Laboratories, Inc., USA). We have found that cavitation effect combined with 10 mg/kg Doxil○R can significantly increase doxorubicin accumulation in tumor tissue 24 hour after treatment as compared to injecting Doxil○R only. Keeping the treatment for a duration time (at least 4 weeks), the effect of cavitaiton on tumor tissue becomes more obvious and able to inhibit big tumor (volume>100 mm3) growth effectively(p<.05). In addition, 5 mg/kg Doxil○R injection with cavitation has significant impact (p<.05) on inhibiting the growth of small tumors (volume<30 mm3). This study also investigated treatment effects to mouse tumors with applying additional focused ultrasound.