The comparison of the dynamics of Ca and bleomycin intracellular delivery after cell sonoporation and electroporation in vitro.

Ca, in combination with SP or EP, induces cell cytotoxicity much faster compared to BLM. The application of BLM in combination with, SP or EP, reaches the level of cell death, induced by similar combination with Ca, only after 72 h. The methods of SP and EP were calibrated according to the level of differential cytotoxicity, determined after 6 days (using cell clonogenic assay). The combination of Ca SP induces cell death faster than Ca EP - after Ca SP it increases to a maximum level after 15 min and remains constant for up to 6 days, while the cytotoxic efficiency after Ca EP increases to the level of Ca SP only after 72 h. The combination of BLM SP shows a very similar dynamics to BLM EP - both reach maximal level of cytotoxicity after 48-72 h. Ca and BLM in combination with SP have shown similar levels of cytotoxicity at higher acoustic pressures (≥250 kPa); therefore, Ca SP can be used to induce immediate and maximal level of cytotoxic effect. The faster cytotoxic efficiency of Ca in combination with SP than EP was determined to be due to the involvement of microbubble inertial cavitation.