In Vitro Experimental and Numerical Studies on the Preferential Ablation of Chemo-Resistant Tumor Cells Induced by High-Voltage Nanosecond Pulsed Electric Fields.

Abstract

UNLABELLED: Chemoresistance causes tumor recurrence and metastasis, resulting in poor clinical outcomes and low survival, and has been considered an obstacle to tumor therapy. The development of novel therapeutic approaches that can effectively kill chemoresistant tumor cells (CRTCs) is therefore critical to overcoming these obstacles. OBJECTIVE: Here, we introduce an emerging physical feature-based therapeutic approach based on nanosecond pulsed electric fields (nsPEFs). The goal of this study is to investigate the effect of nsPEFs on CRTCs. METHODS: The cell viability, ablation effects on a 3D-cultured scaffold, and lethal thresholds of nsPEFs were evaluated according to fluorescence staining assays. RESULTS: nsPEF treatment preferentially affected chemoresistant cells (A549/CDDP) with a higher cell viability inhibition ability/cell death rate, larger ablation area, and lower ablation threshold compared to their respective homologous tumor cells (A549). The experimental and theoretical studies suggested that nsPEFs displayed selective behavior toward intracellular structures. With this selective character, nsPEFs can induce higher electroporation effects (e.g., higher pore number, larger electroporation area, and faster fluorescence dissipation on the nuclear envelope) on CRTCs due to their larger nuclear size and cell membrane capacitance. CONCLUSION: These findings demonstrated that nsPEFs induced preferential ablation of CRTCs over their respective homologous tumor cells. SIGNIFICANCE: This study provides an experimental and theoretical basis for the study of killing CRTCs by electrical treatments and suggests potential applications in the optimization of novel anti-chemoresistance methods.