Muratori Claudia, Pakhomov Andrei G, Xiao Shu, Pakhomova Olga N
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, VA 23508, USA.
Sci Rep. 2016 Mar 18;6:23225. doi: 10.1038/srep23225.
Previous studies reported a delayed increase of sensitivity to electroporation (termed "electrosensitization") in mammalian cells that had been subjected to electroporation. Electrosensitization facilitated membrane permeabilization and reduced survival in cell suspensions when the electric pulse treatments were split in fractions. The present study was aimed to visualize the effect of sensitization and establish its utility for cell ablation. We used KLN 205 squamous carcinoma cells embedded in an agarose gel and cell spheroids in Matrigel. A local ablation was created by a train of 200 to 600 of 300-ns pulses (50 Hz, 300-600 V) delivered by a two-needle probe with 1-mm inter-electrode distance. In order to facilitate ablation by engaging electrosensitization, the train was split in two identical fractions applied with a 2- to 480-s interval. At 400-600 V (2.9-4.3 kV/cm), the split-dose treatments increased the ablation volume and cell death up to 2-3-fold compared to single-train treatments. Under the conditions tested, the maximum enhancement of ablation was achieved when two fractions were separated by 100 s. The results suggest that engaging electrosensitization may assist in vivo cancer ablation by reducing the voltage or number of pulses required, or by enabling larger inter-electrode distances without losing the ablation efficiency.
先前的研究报道，接受过电穿孔的哺乳动物细胞对电穿孔的敏感性会延迟增加（称为“电敏化”）。当电脉冲处理被分成多个部分时，电敏化促进了细胞膜通透性，并降低了细胞悬液中的存活率。本研究旨在观察敏化的效果，并确定其在细胞消融中的效用。我们使用了包埋在琼脂糖凝胶中的KLN 205鳞状癌细胞和基质胶中的细胞球体。通过两针探头（电极间距1毫米）施加一系列200至600个300纳秒的脉冲（50赫兹，300 - 600伏）来产生局部消融。为了通过利用电敏化促进消融，该系列脉冲被分成两个相同的部分，以2至480秒的间隔施加。在400 - 600伏（2.9 - 4.3千伏/厘米）下，与单次脉冲系列处理相比，分剂量处理使消融体积和细胞死亡增加了2至3倍。在所测试的条件下，当两个部分间隔100秒时，实现了最大的消融增强效果。结果表明，利用电敏化可能有助于体内癌症消融，通过降低所需的电压或脉冲数量，或者通过在不损失消融效率的情况下实现更大的电极间距。
