Nanosecond pulses targeting intracellular ablation increase destruction of tumor cells with irregular morphology.

The decrease in killing sensitivity of the cell membrane to microsecond pulse electric fields (μs-PEFs) is ascribed mainly to the aberrant morphology of cancer cells, with clear statistical correlations observed between cell size and shape defects and the worsening of the electrical response to the PEF. In this paper, nanosecond pulsed electric fields (ns-PEFs) inducing the nucleus effect and μs-PEFs targeting the cell membrane were combined to enhance destruction of irregular cells. The fluorescence dissipation levels of the nuclear membrane and cell membrane exposed to the μs, ns, and ns + μs pulse protocols were measured and compared, and a dynamic electroporation model of irregular cells was established by the finite element software COMSOL. The results suggest that the cell membrane disruption induced by μs-PEFs is worse for extremely irregular cells and depends strongly on cellular morphology. However, the nuclear membrane disruption induced by ns-PEFs does not scale with irregularity, suggesting the use of a combination of ns-PEFs with μs-PEFs to target the nuclear and cell membranes. We demonstrate that ns + μs pulses can significantly enhance the fluorescence dissipation of the cell and nuclear membranes. Overall, our findings indicate that ns + μs pulses may be useful in the effective killing of irregular cells.