Electrosensitization assists cell ablation by nanosecond pulsed electric field in 3D cultures.
Electrosensitization assists cell ablation by nanosecond pulsed electric field in 3D cultures.
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DOI：
10.1038/srep23225
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发表时间：
2016-03-18
影响因子：
4.6
通讯作者：
Pakhomova ON
中科院分区：
文献类型：
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作者：
Muratori C;Pakhomov AG;Xiao S;Pakhomova ON
以前的研究报道，在哺乳动物细胞中，电穿孔的敏感性延迟增加(称为“电敏化”)。当电脉冲处理被分成几个部分时，电敏化促进了膜的通透性，并降低了细胞悬浮液中的存活率。本研究的目的是使敏化的效果可视化，并确定其在细胞消融中的作用。我们使用KLN 205鳞癌细胞包埋在琼脂糖凝胶中和细胞球体在Matrigel中。局部消融是由电极间距离为1 mm的双针探头发出的200~600个300 ns脉冲(50 Hz，300~600 V)产生的。为了通过电敏化来促进消融，列车被分成两个相同的部分，施加2到480%的S间隔。在4 0 0~6 0 0 V(2.9~4.3 kV/cm)条件下，分次给药组的消融体积和细胞死亡率比单次给药组高2~3倍。在实验条件下，当两组分被100 S分离时，消融效果最好。这一结果表明，电敏化可能通过减少所需的电压或脉冲数，或在不损失消融效率的情况下，实现更大的电极间距离，从而帮助体内肿瘤消融。
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.