High-intensity irreversible electroporation targeting intracellular structures enhance tumor ablation in lung cancer models

Hong Bae Kim, Jin Young Youm, Joon-Mo Yang, Sung Bo Sim

Abstract

This study aimed to optimize irreversible electroporation (IRE) parameters to enhance intracellular injury, specifically targeting nuclear and mitochondrial structures that are insufficiently affected by conventional protocols.

Introduction

Cancer remains a leading cause of morbidity and mortality worldwide, with lung cancer being the most prevalent and aggressive type [1]. Although typical therapies, such as surgery, chemotherapy, and radiation, have been effective, their limitations, including substantial side effects and incomplete tumor ablation, necessitate the development of alternative approaches [2].

Materials and methods

To precisely assess the electric field distribution, particularly field heterogeneity near electrode surfaces and edges, we used COMSOL Multiphysics (version 5.4; COMSOL, Stockholm, Sweden) to numerically simulate electric field intensity across voltages ranging from 400 to 2,400 V around aluminum plate electrodes (Cuvette Plus, 4-mm gap, 800 lug, BTX, Massachusetts, USA).

Results

Fig 1 showed that the electric field distribution and thermal happening in the cuvette. The numerical simulations demonstrated the distribution and intensity of the electric field generated at different applied electric field strengths of 1000 V/cm (400 V), 4000 V/cm (1600 V), and 5000 V/cm (2000 V) within the electroporation cuvette setup (a).

Discussion

In this study, we demonstrated that high electric field intensity of 4000 V/cm overcomes critical limitations of conventional IRE by achieving complete cellular ablation through extensive damage to both membrane and intracellular compartments. Our iso-energetic comparison revealed that field intensity, not total electrical energy, is the primary determinant of treatment outcome, addressing the fundamental challenge of tissue heterogeneity-induced electric field distribution distortions.

Acknowledgments

The authors would like to thank C.Y. and M.Y. for their assistance with the experiments.

Citation: Kim HB, Youm JY, Yang J-M, Sim SB (2026) High-intensity irreversible electroporation targeting intracellular structures enhance tumor ablation in lung cancer models. PLoS One 21(4): e0346472. https://doi.org/10.1371/journal.pone.0346472

Editor: Roy P. Planalp, University of New Hampshire, UNITED STATES OF AMERICA

Received: June 13, 2025; Accepted: March 19, 2026; Published: April 22, 2026

Copyright: © 2026 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: This research was funded by the National Research Foundation of Korea, grant number 2022R1F1A1075102 and 2022R1F1A1072398, and by Tech Incubator Program for Startup (RS-2023-00303400) of Ministry of SMEs and Startups. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.