Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields
Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields
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DOI：
10.1177/153303460900800406
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发表时间：
2009-08-01
影响因子：
2.8
通讯作者：
Weaver, James C.
中科院分区：
文献类型：
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作者：
Esser, Axel T.;Smith, Kyle C.;Weaver, James C.
通过大纳秒脉冲电场进行的局部和无药物实体肿瘤消融导致所有细胞膜的超电穿孔，并已观察到通过凋亡触发非热细胞死亡。为了建立基于孔的效应作为诱导细胞凋亡的潜在机制，我们使用具有不规则形状的肝细胞的多细胞系统模型（空间尺度100 μ m）和多尺度肝组织模型（空间尺度200 mm）。多细胞模型的孔直方图表明，由于纳秒电场脉冲，仅存在纳米尺寸的孔。质膜中孔的数量使得纳秒电场脉冲期间的平均组织电导甚至高于较长的不可逆电穿孔脉冲。然而，它表明，这些纳米尺寸的孔，虽然很多，只显着改变细胞膜的渗透性小离子，但不较大的分子。纳秒脉冲电场的肿瘤消融导致小到中等的温度升高。因此，通过细胞凋亡触发细胞死亡的潜在机制必须是非热电相互作用，推测导致与长得多的不可逆电穿孔脉冲不同的离子和分子转运。
Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 pm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.