Enhanced mechanical damage to in vitro cancer cells by high-intensity-focused ultrasound in the presence of microbubbles and titanium dioxide
To evaluate in vitro the feasibility of therapeutic high-intensity-focused ultrasound (HIFU) combined with microbubbles and titanium dioxide (TiO2).
Oral squamous cell carcinoma cells (HSC-2) were sonicated using a HIFU transducer with a resonant frequency of 3.5 MHz, 30 mm in diameter, and focal length of 50 mm. The ultrasound intensity was 210 W/cm2, and two pulses (0.5 s each) were sonicated for each cell sample (9 × 104 cells per well). Immediately after HIFU, the viable cells were measured by an automated cell counter. The survival rate was measured in the presence of microbubbles (Sonazoid) and peroxo titania-silica (R-P-TS) or anatase titania-silica (R-A-TS) TiO2.
Cell viability immediately following sonication in the presence of TiO2 (R-A-TS) and TiO2 (R-P-TS) was 65.5 ± 0.7 and 59.4 ± 3.3 %, respectively. A marked decrease in cell viability was seen when microbubbles were added to the above cell conditions. Specifically, cell viability decreased to 14.0 ± 0.1 and 4.4 ± 0.9 % when microbubbles were added to samples containing TiO2 (R-A-TS) and TiO2 (R-P-TS), respectively.
Immediate in vitro cell killing was observed with short pulsed duration HIFU sonication with a combination of microbubbles and TiO2. This finding suggests that TiO2 could have caused enhanced mechanical cell destruction by microbubbles.
KeywordsHigh-intensity-focused ultrasound (HIFU) Titanium dioxide Microbubbles Cell damage
This study was supported in part by the Japanese Society of Ultrasound in Medicine 2013 Research Grant.
Conflict of interest
Katsuro Tachibana, Hitomi Endo, Loreto Feril, Seyedeh Moosavi Nejad, Hiromasa Takahashi, Kyoichi Narihira, and Toshihiro Kikuta all declare that they have no conflict of interest.
This article does not contain any experiments with human or animal subjects performed by any of the authors.