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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The phenomenon known as bipolar cancellation is observed when biphasic nanosecond electric field pulses are used, which results in reduced electroporation efficiency when compared to unipolar pulses of the same parameters. Basically, the negative phase of the bipolar pulse diminishes the effect of the positive phase. Our study aimed to investigate how bipolar cancellation affects Ca2+ electrochemotherapy and cellular response under varying electric field intensities and pulse durations (3–7 kV/cm, 100, 300, and 500 ns bipolar 1 MHz repetition frequency pulse bursts, n = 100). As a reference, standard microsecond range parametric protocols were used (100 µs × 8 pulses). We have shown that the cancellation effect is extremely strong when the pulses are closely spaced (1 MHz frequency), which results in a lack of cell membrane permeabilization and consequent failure of electrochemotherapy in vitro. To validate the observations, we have performed a pilot in vivo study where we compared the efficacy of monophasic (5 kV/cm × ↑500 ns × 100) and biphasic sequences (5 kV/cm × ↑500 ns + ↓500 ns × 100) delivered at 1 MHz frequency in the context of Ca2+ electrochemotherapy (B16-F10 cell line, C57BL/6 mice, n = 24). Mice treated with bipolar pulses did not exhibit prolonged survival when compared to the untreated control (tumor-bearing mice); therefore, the bipolar cancellation phenomenon was also occurrent in vivo, significantly impairing electrochemotherapy. At the same time, the efficacy of monophasic nanosecond pulses was comparable to 1.4 kV/cm × 100 µs × 8 pulses sequence, resulting in tumor reduction following the treatment and prolonged survival of the animals.

Details

Title
The Effects of Bipolar Cancellation Phenomenon on Nano-Electrochemotherapy of Melanoma Tumors: In Vitro and In Vivo Pilot
Author
Mickevičiūtė, Eglė 1   VIAFID ORCID Logo  ; Radzevičiūtė-Valčiukė, Eivina 1   VIAFID ORCID Logo  ; Malyško-Ptašinskė, Veronika 2   VIAFID ORCID Logo  ; Malakauskaitė, Paulina 1 ; Lekešytė, Barbora 1   VIAFID ORCID Logo  ; Rembialkowska, Nina 3   VIAFID ORCID Logo  ; Kulbacka, Julita 4   VIAFID ORCID Logo  ; Tunikowska, Joanna 5 ; Novickij, Jurij 2 ; Novickij, Vitalij 1   VIAFID ORCID Logo 

 Department of Immunology and Bioelectrochemistry, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania; [email protected] (E.M.); [email protected] (E.R.-V.); [email protected] (P.M.); [email protected] (B.L.); [email protected] (J.K.); Faculty of Electronics, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania; [email protected] (V.M.-P.); [email protected] (J.N.) 
 Faculty of Electronics, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania; [email protected] (V.M.-P.); [email protected] (J.N.) 
 Department of Molecular and Cellular Biology, Wroclaw Medical University, 50-367 Wroclaw, Poland; [email protected] 
 Department of Immunology and Bioelectrochemistry, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania; [email protected] (E.M.); [email protected] (E.R.-V.); [email protected] (P.M.); [email protected] (B.L.); [email protected] (J.K.); Department of Molecular and Cellular Biology, Wroclaw Medical University, 50-367 Wroclaw, Poland; [email protected] 
 Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland; [email protected] 
First page
9338
Publication year
2024
Publication date
2024
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3104099487
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.