Self focusing acoustic transducer (SFAT) with 10-mm focal length for cancer-specific localized cytolysis of 3D cell spheroids in 3D Matrigel

This paper reports three-dimensional (3D) localized cytolysis of cell spheroids by Self Focusing Acoustic Transducers (SFAT) with 10 mm focal length. In previous studies, it has been demonstrated that an SFAT with 800 μm focal length caused localized cytolysis on monolayer cells. Since practical ultrasonic cancer therapeutics are usually performed in a 3D biological environment, an SFAT having a long penetration depth and focusing acoustic energy at 10 mm within an area of 160 μm in diameter has been designed and fabricated. Also, the acoustic intensity thresholds (AITs) of spheroids for cancer-specific cytolysis of malignant cells (breast cancer MCF-7 and prostate cancer 22RV1) are investigated. According to experiments with the spheroids in 3D Matrigel environment, the crosslinks between Matrigel and spheroids greatly increase AITs of 22RV1 and MCF-7 cell spheroids from 0.11 W/cm2 to 11.10 ~ 15.14 W/cm2. In addition, in both “unsolidified” (without crosslink) and solidified (with crosslink) Matrigel environments, spheroids of non-malignant cell line MCF-10A are not lysed even with two to three times higher acoustic intensities than the AITs of MCF-7. Therefore, the general trend associating a lower AIT with a more malignant still stands for MCF-7 and MCF-10A 3D spheroids in 3D Matrigel environment.