Application of bioimpedance spectroscopy to characterize chemoresistant tumor cell selectivity of nanosecond pulse stimulation.

ABSTRACT

The discriminating effects of nanosecond pulsed electric fields (nsPEFs) between chemoresistant tumor cells (CRTCs) and their respective homologous chemosensitive tumor cells (CSTCs) were investigated based on bioimpedance spectroscopy (BIS). The electrical properties of individual untreated cells were determined by fitting the impedance spectra to an equivalent circuit model and then using aided simulations to calculate the nuclear envelope transmembrane potential (nTMP) and electroporation area on the nuclear envelope. Additionally, fluorescence staining assays of cell monolayers after nanopulse stimulation (80 pulses, 200 ns, 3 kV) were conducted to validate the simulation results. The staining results indicated that CRTCs showed a larger ablation area and lower lethal threshold compared to CSTCs after exposure to the same nsPEF energy, which was in accordance with the higher nTMP and larger electroporation area calculated for CRTCs. The increase in the lethal effects of nsPEFs on CRTCs compared to CSTCs mainly resulted from the superposition of the changes in the electrical properties and nuclear size. The work shows that BIS can distinguish CRTCs and CSTCs and the corresponding nsPEF effects, suggesting potential applications for the optimization of novel anti-chemoresistance methods, including nsPEF-treatments.