University of Ljubljana, Faculty of Electrical Engineering, Tržaška cesta 25, 1000 Ljubljana, Slovenia.
Jožef Stefan Institute, Department of Environmental Sciences, Jamova cesta 39, 1000 Ljubljana, Slovenia.
Bioelectrochemistry. 2021 Aug;140:107798. doi: 10.1016/j.bioelechem.2021.107798. Epub 2021 Mar 9.
Nanosecond electric pulses have several potential advantages in electroporation-based procedures over the conventional micro- and millisecond pulses including low level of heating, reduced electrochemical reactions and reduced muscle contractions making them alluring for use in biomedicine and food industry. The aim of this study was to evaluate if nanosecond pulses can enhance the cytotoxicity of chemotherapeutics bleomycin and cisplatin in vitro and to quantify metal release from electrodes in comparison to 100 μs pulses commonly used in electrochemotherapy. The effects of nanosecond pulse parameters (voltage, pulse duration, number of pulses) on cell membrane permeabilization, resealing and on cell survival after electroporation only and after electrochemotherapy with bleomycin and cisplatin were evaluated on Chinese hamster ovary cells. Application of permeabilizing nanosecond pulses in combination with chemotherapeutics resulted in successful cell kill. Higher extracellular concentrations of bleomycin - but not cisplatin - were needed to achieve the same decrease in cell survival with nanosecond pulses as with eight 100 μs pulses, however, the tested bleomycin concentrations were still considerably lower compared to doses used in clinical practice. Decreasing the pulse duration from microseconds to nanoseconds and concomitantly increasing the amplitude to achieve the same biological effect resulted in reduced release of aluminum ions from electroporation cuvettes.
纳秒电脉冲在基于电穿孔的程序中相对于传统的微秒和毫秒脉冲具有几个潜在的优势，包括低加热水平、减少的电化学反应和减少的肌肉收缩，这使得它们在生物医学和食品工业中具有吸引力。本研究的目的是评估纳秒脉冲是否可以增强化疗药物博来霉素和顺铂的细胞毒性，体外并与电化学治疗中常用的 100 μs 脉冲相比，量化电极的金属释放。研究了纳秒脉冲参数（电压、脉冲持续时间、脉冲数）对细胞膜通透性、再封闭以及电穿孔后仅和电穿孔后与博来霉素和顺铂进行电化学治疗后细胞存活的影响，在中华仓鼠卵巢细胞上进行了评估。应用致孔纳秒脉冲与化疗药物联合使用可成功杀死细胞。与 8 个 100 μs 脉冲相比，需要更高的细胞外博来霉素浓度才能达到相同的细胞存活率降低效果，但测试的博来霉素浓度仍远低于临床实践中使用的剂量。将脉冲持续时间从微秒缩短到纳秒，并同时增加幅度以达到相同的生物学效果，可减少电穿孔小瓶中铝离子的释放。
