ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
This article is part of the Research TopicAdvances in Nanotechnology and Multi-Targeting Strategies for Effective Cancer ChemotherapyView all articles
Application of Nisin as a Potential Drug Candidate for Electrochemotherapy
Provisionally accepted
Olga Michel1,2*
Barbora Lekešytė1,3
Veronika Malyško-Ptašinskė1,3Arnoldas Morozas1Paulina Malakauskaitė1,3Eglė Mickevičiūtė1,3Augustinas Želvys1,3
JUSTINAS IVASKA1
Julita Kulbacka1,2
Vitalij Novickij1,3- 1State Research Institute Center for Innovative Medicine, Vilnius, Lithuania
- 2Uniwersytet Medyczny im Piastow Slaskich we Wroclawiu, Wrocław, Poland
- 3Vilniaus Gedimino technikos universitetas, Vilnius, Lithuania
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Electroporation (EP) is a technique that transiently increases the permeability of the cell membrane through the application of high-voltage electric pulses, facilitating the intracellular delivery of therapeutic agents or the selective ablation of cells. Combination of EP with cytotoxic drugs - most commonly bleomycin or cisplatin - is termed electrochemotherapy (ECT), which markedly enhances drug efficacy and permits targeted, locally controlled treatment with reduced systemic exposure. Currently, in addition to microsecond (μs) pulses, nanosecond (ns) pulses are being proposed for clinical use to mitigate certain ECT-associated side effects. However, achieving robust permeabilization with nsPEF typically requires higher electric fields. Nisin is a polycyclic antibacterial peptide with anticancer potential that can be leveraged in this context. To date, the permeabilizing properties of nisin have been employed alongside an external electric field exclusively in bacterial systems and artificial membranes. In this study, we investigated the impact of nisin on membrane permeabilization, resealing, and viability of 4T1 breast cancer cells exposed to microsecond and nanosecond electric pulses of varying field strengths and pulse frequencies. Across all experimental conditions, nisin reduced the threshold voltage necessary for effective permeabilization and elevated treatment-induced cell mortality. Since nisin is non-toxic by itself, it makes a good candidate for electrochemotherapy, potentially supporting its wider clinical application in the future.
Keywords: Nisin, nsPEF, µsPEF, Electroporation, breast cancer, ECT
Received: 21 Aug 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Michel, Lekešytė, Malyško-Ptašinskė, Morozas, Malakauskaitė, Mickevičiūtė, Želvys, IVASKA, Kulbacka and Novickij. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Olga Michel, michel.olga.maria@gmail.com
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