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纳秒电穿孔化疗联合博来霉素或多柔比星:脉冲幅度、持续时间和脉冲频率的影响。

Nanosecond electrochemotherapy using bleomycin or doxorubicin: Influence of pulse amplitude, duration and burst frequency.

机构信息

State Research Institute Centre for Innovative Medicine, Department of Immunology, Vilnius, Lithuania; Faculty of Electronics, Vilnius Gediminas Technical University, Vilnius, Lithuania.

Faculty of Electronics, Vilnius Gediminas Technical University, Vilnius, Lithuania.

出版信息

Bioelectrochemistry. 2022 Dec;148:108251. doi: 10.1016/j.bioelechem.2022.108251. Epub 2022 Aug 27.

DOI:10.1016/j.bioelechem.2022.108251
PMID:36049422
Abstract

Electroporation is a pulsed electric field (PEF) induced phenomenon, which effectiveness varies dependent on pulse parameters. This work focuses on nano-electrochemotherapy with bleomycin and doxorubicin to derive protocols as effective as European Standard Operating Procedures on Electrochemotherapy (ESOPE), which employ conventional microsecond range pulses. As a model, murine Lewis lung carcinoma (LLC1) cell line was used. The effects of pulse duration (100-500 ns), PEF amplitude (6-10 kV/cm) and pulse repetition frequency (10 kHz, 100 kHz, 1 MHz) were studied. A total of 75 ns protocol variations have been used. For detection of cell permeabilization, Yo-Pro-1 and flow cytometry were employed. Cell viability was evaluated 24-, 48-, or 72-hours post-electroporation. Nanosecond parametric protocols resulting in comparable treatment efficiency as ESOPE (1.3 kV/cm × 100 μs × 8) have been proposed. It was shown that high-frequency nanosecond electrochemotherapy with bleomycin or doxorubicin could be an alternative for established ESOPE protocols.

摘要

电穿孔是一种脉冲电场(PEF)诱导的现象,其效果取决于脉冲参数。本工作专注于使用博来霉素和阿霉素的纳秒电化学疗法,以制定与采用常规微秒范围脉冲的欧洲电化学疗法标准操作规程(ESOPE)一样有效的方案。采用小鼠 Lewis 肺癌(LLC1)细胞系作为模型。研究了脉冲持续时间(100-500ns)、PEF 幅度(6-10kV/cm)和脉冲重复频率(10kHz、100kHz、1MHz)的影响。总共使用了 75ns 的协议变化。为了检测细胞通透性,使用了 Yo-Pro-1 和流式细胞术。在电穿孔后 24、48 或 72 小时评估细胞活力。提出了与 ESOPE(1.3kV/cm×100μs×8)相当的纳秒参数协议,这些协议可以达到类似的治疗效果。结果表明,使用博来霉素或阿霉素的高频纳秒电化学疗法可能是既定 ESOPE 方案的替代方案。

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