20.500.12556/RUL-170893 Reassessing lidocaine as an electroporation sensitizer in vitro High-intensity pulsed electric fields induce transient increase in membrane permeability, a phenomenon known as electroporation, with broad applications in medicine, including electrochemotherapy (ECT), gene electrotransfer and tissue ablation. As electroporation technologies become increasingly established in clinical practice, understanding how commonly used pharmacological agents influence treatment outcomes is gaining importance. Lidocaine, a widely used local anesthetic and ion channel modulator, has recently been investigated as a potential sensitizer to enhance the efficacy of electroporation. Here, we examined the effects of lidocaine on membrane permeabilization and cell viability using standard 8 × 100 µs ECT pulses across four cell lines: melanoma B16-F1, myoblast C2C12, CHO-K1 cells with low ion channel expression, and NS-HEK cells with stable ▫$Na_v$▫1.5 expression. We show that 10 mM lidocaine has only modest effects on electroporation outcomes, while 35 mM considerably lowers the electric field threshold for irreversible electroporation by 25–40% in melanoma cells. However, concentrations of even 10 mM exceed those reported in tissues following local administration of lidocaine. This questions the clinical relevance of lidocaine’s sensitization effect and warrants further investigation. Our study also highlights the importance of evaluating drug–electroporation interactions under rigorously controlled experimental conditions to ensure meaningful translation into clinical applications. electroporation sensitization electropermeabilization cell survival lidocaione melanoma cells elektroporacija senzitizacija preživetje celic lidokain celice melanoma true false true Angleški jezik Slovenski jezik Članek v reviji 2025-07-21 10:53:41 2025-07-21 10:53:47 2025-07-22 04:15:59 0000-00-00 00:00:00 2025 0 0 15 str. 15, art. 25593 2025 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 602.621 2045-2322 10.1038/s41598-025-11695-3 243181571 s41598-025-11695-3.pdf s41598-025-11695-3.pdf 1 D744E32A8D8776AD6CEB930F8067A26C 0d5fc9ea5f40468eef692988900a1787f3ab68c65dfcb1f11cca79b19b85b022 963ca242-6610-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=213165 https://www.nature.com/articles/s41598-025-11695-3 1 35f8edcd-6610-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=213163 Fakulteta za elektrotehniko 0 0 0