Electrolytic ablation enables cancer cell targeting through pH modulation

Abstract

Minimally invasive ablation strategies enable locoregional treatment of tumors. One such strategy, 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.

Changes in pH as a result of galvanic currents used in percutaneous needle electrolysis

“…The literature on this subject explains that when two electrodes are immersed in a conductive medium and a direct current (galvanic current) passes between them, electrochemical reactions take place around the electrodes and in the medium containing the same. 5 The present study found that the pH change only takes place in a simple solution of NaCl. Using normal oxygenated Ringer's solution, no pH change was observed, neither did this occur with a live sample.…”

“…6 A pioneering work by Li et al 9 applied a GC protocol of 8.5 Volts at 30 mA during 69 minutes, obtaining changes in the concentrations of Na þ and K þ ions in the cathode (pH ¼ 12.9) and the Cl À concentrations in the anode (pH ¼ 2.1). Subsequently, several papers were published 5,7,10 that considered the pH change as being the main mechanism of necrosis in tissues treated with electrical currents. This change in pH within the human body requires a temporary application of $30 minutes to achieve these effects and also requires both electrodes to be present in the treated tissue.…”

An Ultrasonically Powered Implantable Microprobe for Electrolytic Ablation

“…We used a 0.7% (w/v) agarose gel with a pH indicator (i.e., phenol red) for visualization of the ablation zone. Agarose gel was used since it is electrically neutral and mechanically stable at room temperature; this gel is a well-established phantom to assess EA 2,36,37 . The pH in the agarose gel was adjusted to a physiological pH of 7.4 by adding 0.9 wt/% sodium chloride.…”

“…Local thermal ablation using insertable RF or microwave probes has also been used to destroy solid tumors in cases where the tumor is deemed to be nonresectable (e.g., liver or pancreatic tumors close to a sensitive anatomical structure) 1 . Although clinically accepted, thermal ablation methods face limitations in cases where the tumor is located near a major blood vein, for which collateral thermal damage is unacceptable [1][2][3] . Other ablation methods using laser sources, high-intensity focused ultrasound (HIFU), and cold (cryo-ablation) have also been proposed and are currently at various stages of development and clinical trials [4][5][6] .…”

Advances in the Electrochemical Treatment of Cancers and Tumors: Exploring the Current Trends, Advancements, and Mechanisms of Electrolytic Tumor Ablation

“…More recently, research conducted by Perkons et al [13] attempted to identify additional parameters by which EChT was able to destroy tumor growth. Three parameters were tested based the hypothesis of prior works: temperature, the presence of reactive oxygen species (ROS), and localized changes in pH value.…”