Electroporation-induced electrosensitization.
Electroporation-induced electrosensitization.
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DOI：
10.1371/journal.pone.0017100
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发表时间：
2011-02-09
期刊：
影响因子：
3.7
通讯作者：
Pakhomov AG
中科院分区：
文献类型：
--
作者：
Pakhomova ON;Gregory BW;Khorokhorina VA;Bowman AM;Xiao S;Pakhomov AG
电穿孔是一种通过电脉冲（EP）破坏细胞膜完整性的方法。电建模被广泛用于解释和研究电穿孔，但即使是最先进的模型也显示出有限的预测能力。没有研究将电穿孔的生物学后果解释为改变细胞对即将到来的 EP 的敏感性的因素。我们首先关注 EP 速率对哺乳动物细胞膜透化和致死作用的作用。速率从 0.001 到 2,000 Hz 变化，同时保持其他参数恒定（2 到 3,750 个脉冲，持续时间 60 ns 到 9 µs，1.8 到 13.3 kV/cm）。所有 EP 处理的效率在高速率时都是最小的，并且当速率降低到某个值以下时开始逐渐增加。尽管该值范围很广（0.1-500 Hz），但它始终对应于接近 10 秒的总治疗持续时间。我们进一步发现，无论 EP 速率如何，较长的暴露时间都更有效，并且将高速率 EP 序列分成两部分并延迟 1-5 分钟，可以将效果增强数倍。对于不同的实验条件，EP 引发了对 EP 的延迟和逐渐的敏化。当多脉冲照射的一部分被传递到已经敏化的细胞时，总体效果显着增加。由于致敏作用，只需增加暴露时间即可将 EP 处理细胞的致死率从 0% 提高到 90%，或者可以将暴露剂量减少两倍而不降低效果。电穿孔的许多应用可以受益于考虑敏化，通过组织暴露来最大化敏化（例如，用于灭菌），或者对于其他应用，完全或部分避免它。特别是，基于电穿孔的疗法（电化学疗法、基因疗法、肿瘤消融）的有害副作用包括抽搐、疼痛、心颤和热损伤。敏化可潜在地用于减少这些副作用，同时保持或提高治疗效率。
Electroporation is a method of disrupting the integrity of cell membrane by electric pulses (EPs). Electrical modeling is widely employed to explain and study electroporation, but even most advanced models show limited predictive power. No studies have accounted for the biological consequences of electroporation as a factor that alters the cell's susceptibility to forthcoming EPs. We focused first on the role of EP rate for membrane permeabilization and lethal effects in mammalian cells. The rate was varied from 0.001 to 2,000 Hz while keeping other parameters constant (2 to 3,750 pulses of 60-ns to 9-µs duration, 1.8 to 13.3 kV/cm). The efficiency of all EP treatments was minimal at high rates and started to increase gradually when the rate decreased below a certain value. Although this value ranged widely (0.1–500 Hz), it always corresponded to the overall treatment duration near 10 s. We further found that longer exposures were more efficient irrespective of the EP rate, and that splitting a high-rate EP train in two fractions with 1–5 min delay enhanced the effects severalfold. For varied experimental conditions, EPs triggered a delayed and gradual sensitization to EPs. When a portion of a multi-pulse exposure was delivered to already sensitized cells, the overall effect markedly increased. Because of the sensitization, the lethality in EP-treated cells could be increased from 0 to 90% simply by increasing the exposure duration, or the exposure dose could be reduced twofold without reducing the effect. Many applications of electroporation can benefit from accounting for sensitization, by organizing the exposure either to maximize sensitization (e.g., for sterilization) or, for other applications, to completely or partially avoid it. In particular, harmful side effects of electroporation-based therapies (electrochemotherapy, gene therapies, tumor ablation) include convulsions, pain, heart fibrillation, and thermal damage. Sensitization can potentially be employed to reduce these side effects while preserving or increasing therapeutic efficiency.
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影响因子：
5
作者：
Ibey, Bennett L.;Mixon, Dustin G.;Payne, Jason A.;Bowman, Angela;Sickendick, Karl;Wilmink, Gerald J.;Roach, W. Patrick;Pakhomov, Andrei G.
通讯作者：
Pakhomov, Andrei G.
影响因子：
3
作者：
Ibey, Bennett L.;Pakhomov, Andrei G.;Gregory, Betsy W.;Khorokhorina, Vera A.;Roth, Caleb C.;Rassokhin, Mikhail A.;Bernhard, Joshua A.;Wilmink, Gerald J.;Pakhomova, Olga N.
通讯作者：
Pakhomova, Olga N.
DOI：
10.1083/jcb.200708010
发表时间：
2008-03-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Idone V;Tam C;Goss JW;Toomre D;Pypaert M;Andrews NW
通讯作者：
Andrews NW
影响因子：
4.2
作者：
Andre, F. M.;Gehl, J.;Mir, L. M.
通讯作者：
Mir, L. M.
影响因子：
5
作者：
Bilska, AO;DeBruin, KA;Krassowska, W
通讯作者：
Krassowska, W