Augmenting the Electrosensitivity of Tumor Cells by Combining Nanosecond and Microsecond Pulsed Electric Fields

Successful application of the electroporation effect generated by pulsed electric field in clinical minimally invasive tumor therapy has been demonstrated. This study proposes the combination of nanosecond and microsecond pulsed electric fields (ns+μsPEF) to enhance the efficiency of tumor ablation. The human malignant melanoma cells (A375) were used as experimental subjects. Analysis of the combined effects of ns+μsPEFs was conducted by tests involving fluorescence dissipation and cell death at subcellular, cellular, and 2D multicellular scaffolds. The improvement mechanism was elucidated by simulating the electroporation behavior under ns+μsPEFs. Synergy of nanosecond and microsecond pulsed electric fields was shown to effectively target both the cell membrane and intracellular organelles, including the cell nucleus. The ns+μsPEFs can greatly improve the electrosensitivity of tumor cells to the electric stimulus by facilitating the dissipation of fluorescence dispersion from individual cells, thereby boosting the rate of cell death and achieving a broader and less residual ablation region. Furthermore, the electroporation process modeling provided evidence that ns+μsPEFs efficiently increased the pore radii on the cell membrane while preserving the high pore density of the cell nucleus. The research introduces an innovative electroporation method that combines nanosecond and microsecond pulsed electric fields. Simulation and experimental results provide both empirical and theoretical evidence to suggest that this approach can enhance cell destruction and tissue ablation due to the synergistic interaction between the different pulse durations. Consequently, in clinical practice, the use of ns+μsPEFs has the potential to minimize residual tissue after ablation and reduce the duration of treatment sessions.