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Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types
Elena C Gianulis1, Chantelle Labib2, Gintautas Saulis3
1Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA. egianulis@odu.edu.
Abstract:
Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.
Insights
Nanosecond pulsed electric fields (nsPEF) show variable tumor ablation efficacy across cell types. Non-cancerous cells exhibited differential sensitivity, suggesting nsPEF parameter optimization for cancer therapy.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Oncology
Background:
- Nanosecond pulsed electric fields (nsPEF) represent an emerging therapeutic strategy for tumor ablation.
- Understanding differential cellular responses to nsPEF is crucial for optimizing treatment outcomes.
Purpose of the Study:
- To compare the cytotoxicity of nsPEF across various human cancerous and non-cancerous cell lines.
- To investigate the influence of nsPEF parameters on cell survival and identify factors affecting sensitivity.
Main Methods:
- Human cell lines (IMR-32, Hep G2, HT-1080, HPAF-II, BJ, MRC-5) were uniformly treated with 300-ns PEF under controlled conditions.
- Cell survival was assessed across a range of pulse numbers (0-2000 pulses) at 1.8 kV/cm and 50 Hz.
- Alternative nsPEF parameters (9 µs pulse duration, 0.75 kV/cm, 5 Hz) were explored to evaluate selectivity.
Main Results:
- All cell types exhibited three distinct survival regions: initial resistivity, logarithmic decline, and residual resistivity.
- Significant variations in LD50 (lethal dose for 50% of cells) were observed, with differences up to 80-fold.
- Non-cancerous cells were less sensitive than IMR-32 neuroblastoma but more sensitive than other cancer cell lines tested.
- Cytotoxic efficiency did not correlate with cell size, nuclear size, morphology, metabolism, or membrane disruption.
Conclusions:
- nsPEF exhibits differential cytotoxicity across human cell lines, with varying sensitivity observed between cancerous and non-cancerous cells.
- The selectivity of nsPEF ablation can be modulated by adjusting pulse parameters, potentially overcoming cancer cell resistance.
- Further research into mechanisms and cell markers of nsPEF susceptibility is essential for clinical application.
