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首页> 外文期刊>Scientific reports. >Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy
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Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy

机译：短高压脉冲和长低压脉冲的协同组合增强了不可逆的电穿孔功效

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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.
机译：不可逆电穿孔（IRE）使用约100？μs的脉冲电场破坏细胞膜，以进行实体瘤消融。尽管IRE取得了令人鼓舞的初步临床结果，但由于消融区域的体积限制，实施IRE可能会具有挑战性。将短高压脉冲（SHV：1600V，2？μs，1？Hz，20脉冲）与长低压脉冲（LLV：240–480？V，100？μs，1？Hz，60–80脉冲）组合诱导增强IRE功效的协同作用。在这里，研究了细胞的细胞毒性和组织消融。结果表明，将SHV脉冲与LLV脉冲组合使用可更有效地诱导SKOV3细胞死亡，并且与单独使用SHV脉冲或LLV脉冲相比，该组合显着增强了消融区域。特别是，延长SHV和LLV脉冲之间的滞后时间（100？s）会进一步降低细胞活力并增加消融面积。但是，SHV和LLV脉冲的顺序很重要，并且LLVα+βSHV组合不如SHVα+βLLV组合有效。我们提供了一个假设来解释增强的细胞细胞毒性和扩大的消融面积背后的协同效应。这项工作表明，SHV脉冲与LLV脉冲的结合可以用作局部治疗，并且可以在较大的临床前模型和微观机制中进行研究。

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