Sonodynamic Treatment Induces Selective Killing of Cancer Cells in an In Vitro Co-Culture Model

SIMPLE SUMMARY: A review of over six decades of cancer chemotherapies, including recent immunotherapy, reveals partial success in the battle against cancer. One of the main reasons for this slow progress is the failure, by mainstream anticancer treatments, to distinguish between cancer cells and normal cells. For this reason, the aim of our study was to assess if sonodynamic therapy (SDT), a new anticancer approach, can affect cancer cells only, avoiding any harmful effects on normal cells. SDT aims to cure malignant tumors by using a chemical compound (sonosensitizer) triggered by ultrasound exposure. For this purpose, the effects on cancer cells and normal cells, namely HT-29 cells and HDF 106-05 cells, subjected to sonodynamic treatment were investigated. Our results show that, according to different plasma membrane properties of cancer cells and normal cells, a different sonodynamic effect occurs, reaching a remarkable cytotoxic effect on cancer cells only. ABSTRACT: Sonodynamic Therapy (SDT) is a new anticancer strategy based on ultrasound (US) technique and is derived from photodynamic therapy (PDT); SDT is still, however, far from clinical application. In order to move this therapy forward from bench to bedside, investigations have been focused on treatment selectivity between cancer cells and normal cells. As a result, the effects of the porphyrin activation by SDT on cancer (HT-29) and normal (HDF 106-05) cells were studied in a co-culture evaluating cell cytotoxicity, reactive oxygen species (ROS) production, mitochondrial function and plasma membrane fluidity according to the bilayer sonophore (BLS) theory. While PDT induced similar effects on both HT-29 and HDF 106-05 cells in co-culture, SDT elicited significant cytotoxicity, ROS production and mitochondrial impairment on HT-29 cells only, whereas HDF 106-05 cells were unaffected. Notably, HT-29 and HDF 106-05 showed different cell membrane fluidity during US exposure. In conclusion, our data demonstrate a marked difference between cancer cells and normal cells in co-culture in term of responsiveness to SDT, suggesting that this different behavior can be ascribed to diversity in plasma membrane properties, such as membrane fluidity, according to the BLS theory.