Document Type

Article

Publication Date

2025

Publication Title

International Journal of Molecular Sciences

Volume

26

Issue

2

Pages

458 (1-12)

DOI

10.3390/ijms26020458

Abstract

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

Rights

© 2025 by the authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "The raw data supporting the conclusions of this article will be made available by the authors on request."

Original Publication Citation

Pakhomova, O. N., Zivla, E., Silkuniene, G., Silkunas, M., & Pakhomov, A. G. (2025). Potentiation of gelonin cytotoxicity by pulsed electric fields. International Journal of Molecular Sciences, 26(2), 1-12, Article 458. https://doi.org/10.3390/ijms26020458

ORCID

0000-0003-4950-4130 (Pakhomova), 0009-0006-8465-6817 (Zivla), 0000-0001-8436-9718 (Silkuniene), 0000-0002-4568-9265 (Silkunas), 0000-0003-3816-3860 (Pakhomov)

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