Cell Sensitization is Induced by a Wide Range of Permeabilizing Electric Fields

Abstract

Cell sensitization is a phenomenon where increasing the duration of the electroporation treatment has been reported to increase cell permeabilization and decrease cell survival. Cell sensitization can be obtained by splitting one train of pulses in half and delivering the second half of the pulses after a delay. After the first half of the pulses is applied cells become more sensitive to the following electric pulses. Thus, efficiency of the treatment is sustained even if the second half of the pulses is of lower amplitude. In this study, cell sensitization was investigated in a wide range of electric field amplitudes. Twelve pulses of 100 μs were delivered either twelve in one train (one train protocol) or six in the first train and after 5 min another six in the second train (two trains protocol). In both protocols, the electric field of the first six pulses was varied while the electric field of the second six pulses was fixed or vice versa. Stable cell sensitization was obtained with two trains protocol in a wide range of “permeabilizing” electric fields. Cell survival was reduced up to twofold with the two trains protocol in comparison to the one train protocol. Cell sensitization has possible applications in tumor treatment and in soft tissue ablation. In tumor treatment fewer pulses of lower electric field could be applied and electrodes with larger inter-electrode distance could be used while the efficiency of the treatment would be at least as high as obtained now. In the future, research should focus on the still unknown mechanisms of cell sensitization and then extend to 3-dimensional tissue models and tissues.