Electrolytic ablation enables cancer cell targeting through pH modulation

Minimally invasive ablation strategies enable locoregional treatment of tumors. Electrolytic ablation functions through the local delivery of direct current, without thermal effects, facilitating enhanced precision. However, the clinical application of electrolytic ablation is limited by an incompletely characterized mechanism of action. Here we show that acid and base production at the electrodes precipitates local pH changes causing the rapid cell death that underlies macroscopic tumor necrosis at pH > 10.6 or < 4.8. The extent of cell death can be modulated by altering the local buffering capacity and antioxidant availability. These data demonstrate that electrolytic ablation is distinguished from other ablation strategies via its ability to induce cellular necrosis by directly altering the tumor microenvironment. These findings may enable further development of electrolytic ablation as a curative therapy for primary, early stage tumors.

微创消融策略可实现肿瘤的局部区域治疗。电解消融（Electrolytic ablation）通过局部递送直流电发挥作用，且不产生热效应，有助于提升治疗精准度。然而，电解消融的临床应用受限于其尚未完全阐明的作用机制。本研究证实，电极处产生的酸碱可引发局部pH改变，当pH＞10.6或＜4.8时，会诱导快速细胞死亡，这正是肉眼可见肿瘤坏死的核心诱因。细胞死亡的程度可通过调控局部缓冲能力与抗氧化剂可用性进行调节。上述研究数据表明，电解消融与其他消融策略的核心区别在于，它可通过直接改变肿瘤微环境诱导细胞坏死。本研究结果可为将电解消融开发为原发性早期肿瘤根治性治疗手段提供助力。