Abstract
Irreversible electroporation (IRE) uses ~100 μs pulsed electric fields to disrupt cell membranes for solid tumor ablation. Although IRE has achieved exciting preliminary clinical results, implementing IRE could be challenging because of volumetric limitations at the ablation region. Combining short high-voltage (SHV: 1600V, 2 μs, 1 Hz, 20 pulses) pulses with long low-voltage (LLV: 240–480 V, 100 μs, 1 Hz, 60–80 pulses) pulses induces a synergistic effect that enhances IRE efficacy. Here, cell cytotoxicity and tissue ablation were investigated. The results show that combining SHV pulses with LLV pulses induced SKOV3 cell death more effectively, and compared to either SHV pulses or LLV pulses applied alone, the combination significantly enhanced the ablation region. Particularly, prolonging the lag time (100 s) between SHV and LLV pulses further reduced cell viability and enhanced the ablation area. However, the sequence of SHV and LLV pulses was important, and the LLV + SHV combination was not as effective as the SHV + LLV combination. We offer a hypothesis to explain the synergistic effect behind enhanced cell cytotoxicity and enlarged ablation area. This work shows that combining SHV pulses with LLV pulses could be used as a focal therapy and merits investigation in larger pre-clinical models and microscopic mechanisms.
Highlights
Electroporation has been widely used to increase cell membrane permeabilization through pores by employing a high-voltage pulsed electric field[1]
The results showed that cell viability was below 20% by combining short high-voltage (SHV) pulses with long low-voltage (LLV) pulses, while cell viability was maintained above 60% when either SHV pulses or LLV pulses were applied alone
When LLV pulses were applied before SHV pulses, even if a large electroporated area in the cell membrane was created by the SHV pulses, there were no subsequent LLV pulses to contribute to pore expansion
Summary
Electroporation has been widely used to increase cell membrane permeabilization through pores by employing a high-voltage pulsed electric field[1]. A method for tissue ablation was recently proposed based on pulsed electric fields by combining short high-voltage (SHV) pulses with long low-voltage (LLV) pulses to enhance the ablation area. SHV pulses created a large electroporated area that was more susceptible to subsequent LLV pulses, significantly enhancing the ablation area This modality of pulsed electric fields was reported in a previous study to enlarge the ablation area of potato tissue in vitro[42]. The results showed that the liver ablation area was enlarged when the synergetic effect was evoked by combining SHV pulses (2 μs) with LLV (100 μs) pulses compared to when either SHV pulses or LLV pulses were applied alone. The pulsed electric fields that are used may be applied to optimize the current pulsed electric protocols and to enhance the outcome of IRE efficacies
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