School of Electronics and Information, Hangzhou Dianzi University, Hangzhou, 310018, China.
School of Medicine, Imperial College London, London, SW7 2AZ, UK.
Sci Rep. 2022 Oct 27;12(1):18039. doi: 10.1038/s41598-022-22874-x.
Microsecond pulsed electric fields (PEF) have previously been used for various tumour therapies, such as gene therapy, electrochemotherapy and irreversible electroporation (IRE), due to its demonstrated ability. However, recently nanosecond pulsed electric fields (nsPEF) have also been used as a potential tumor therapy via inducing cell apoptosis or immunogenic cell death to prevent recurrence and metastasis by interacting with intracellular organelles. A large proportion of the existing in-vitro studies of nsPEF on cells also suggests cell necrosis and swelling/blebbing can be induced, but the replicability and potential for other effects on cells suggesting a complicated process which requires further investigation. Therefore, this study investigated the effects of pulse width and intensity of nsPEF on the murine melanoma cells (B16) and normal murine fibroblast cells (L929) through electromagnetic simulation and in-vitro experiments. Through examining the evolution patterns of potential difference and electric fields on the intracellular compartments, the simulation has shown a differential effect of nsPEF on normal and cancerous skin cells, which explains well the results observed in the reported experiments. In addition, the modelling has provided a clear evidence that a few hundreds of ns PEF may have caused a mixed mode of effects, i.e. a 'cocktail effect', including cell electroporation and IRE due to an over their threshold voltage induced on the plasma membrane, as well as cell apoptosis and other biological effects caused by its interaction with the intracellular compartments. The in-vitro experiments in the pulse range of the hundreds of nanoseconds showed a possible differential cytotoxicity threshold of electric field intensity between B16 cells and L929 cells.
微秒级脉冲电场 (PEF) 由于其表现出的能力，先前已被用于各种肿瘤治疗，如基因治疗、电化学治疗和不可逆电穿孔 (IRE)。然而，最近纳秒级脉冲电场 (nsPEF) 也已被用作一种潜在的肿瘤治疗方法，通过与细胞内细胞器相互作用诱导细胞凋亡或免疫原性细胞死亡，以防止复发和转移。大量现有的 nsPEF 对细胞的体外研究还表明，可诱导细胞坏死和肿胀/起泡，但对细胞的其他潜在影响的可复制性表明这是一个复杂的过程，需要进一步研究。因此，本研究通过电磁模拟和体外实验，研究了纳秒级脉冲电场的脉冲宽度和强度对小鼠黑色素瘤细胞 (B16) 和正常小鼠成纤维细胞 (L929) 的影响。通过检查细胞内隔室的电位差和电场的演变模式，模拟显示了 nsPEF 对正常和癌变皮肤细胞的不同影响，这很好地解释了报告实验中观察到的结果。此外，该模型提供了一个明确的证据，即几百个纳秒级的 nsPEF 可能会产生混合效应模式，即“鸡尾酒效应”，包括细胞膜上超过其阈值电压诱导的细胞电穿孔和 IRE，以及与细胞内隔室相互作用引起的细胞凋亡和其他生物学效应。在几百纳秒的脉冲范围内进行的体外实验表明，B16 细胞和 L929 细胞之间的电场强度可能存在差异的细胞毒性阈值。
