Synergistic enhancement of irreversible electroporation by silver nanowires in three-dimensional tumor models

Irreversible electroporation (IRE) is an emerging tumor ablation modality that employs high-intensity pulsed electric fields to disrupt cell membranes. However, achieving complete tumor destruction while preserving adjacent critical structures remains a major challenge. In this study, we investigated whether high-aspect-ratio silver nanowires (AgNWs) could enhance IRE efficacy in a three-dimensional hydrogel-based cell model. We systematically evaluated cell viability, ablation area, conductivity, and temperature under various pulse parameters and AgNW concentrations. Increased electric field strength, longer pulse durations, and higher pulse numbers all potentiated the cytotoxic effect. Under identical pulsing conditions, the addition of 70 μg/mL AgNWs expanded the ablation zone by 42.2% ± 7.5%, allowing lower-energy pulse protocols to achieve ablation comparable to that of higher-energy settings. This enhancement was not attributable to changes in bulk conductivity; rather, the nanowires appeared to amplify the local electric field in the vicinity of cells, thereby boosting treatment sensitivity without introducing significant thermal effects. Collectively, these in vitro findings suggest that AgNWs can potentiate IRE ablation at reduced energy levels, offering a promising adjuvant strategy. Nevertheless, further validation through in vivo studies and comprehensive long-term safety assessments is essential prior to any clinical translation.