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The equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an in vitro study Cover

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin − an in vitro study

Radiology and Oncology
Volume 58 (2024): Issue 1 (March 2024)
By:
Open Access
|Feb 2024

Figures & Tables

FIGURE 1.

(A) 50 × 50 HF pulses. From left to right: 50 bursts were applied with a repetition frequency of 1 Hz; one burst with 200 μs total pulse on time and consisted of 50 bipolar pulses; one bipolar pulse of amplitude U consisted of a 2 μs long positive pulse, and a 2 μs long negative pulse (both of voltage U) with a 2 μs long interpulse delay. (B) 8 × 100 μs or 8 × 5 ms monopolar pulse of amplitude U and pulse duration of 100 μs or 5 ms were applied with a repetition frequency of 1 Hz
(A) 50 × 50 HF pulses. From left to right: 50 bursts were applied with a repetition frequency of 1 Hz; one burst with 200 μs total pulse on time and consisted of 50 bipolar pulses; one bipolar pulse of amplitude U consisted of a 2 μs long positive pulse, and a 2 μs long negative pulse (both of voltage U) with a 2 μs long interpulse delay. (B) 8 × 100 μs or 8 × 5 ms monopolar pulse of amplitude U and pulse duration of 100 μs or 5 ms were applied with a repetition frequency of 1 Hz

FIGURE 2.

Schematic of the model that describes electroporation and molecular transport. (A) The equivalent circuit, which considers electroporation (membrane pore/defect formation) to be a two-step process, as depicted in (B). The blue capacitance and resistance represent the intact cell membrane. When the electric field is applied, the cell membrane becomes permeable first to small ions, indicating the first porous state (N) of the membrane represented by green resistance. Then the membrane becomes permeable to small molecules, indicating the second porous state (M) of the membrane represented by magenta resistance. Reproduced from Sweeney et al.56 with permission.
Schematic of the model that describes electroporation and molecular transport. (A) The equivalent circuit, which considers electroporation (membrane pore/defect formation) to be a two-step process, as depicted in (B). The blue capacitance and resistance represent the intact cell membrane. When the electric field is applied, the cell membrane becomes permeable first to small ions, indicating the first porous state (N) of the membrane represented by green resistance. Then the membrane becomes permeable to small molecules, indicating the second porous state (M) of the membrane represented by magenta resistance. Reproduced from Sweeney et al.56 with permission.

FIGURE 3.

Cell survival (solid) and cell membrane permeability (dashed) as a function of the electric field when (A) 50 × 50 HF pulses; (B) 8 × 100 μs pulses; (C) 8 × 5 ms pulses are used. The chosen optimal electric fields are encircled. Each data point presents the mean ± standard deviation from 3–4 experiments. * = statistically significant differences from control (p < 0.05) performing one-way ANOVA if the normality test passed or otherwise ANOVA on ranks. The light blue, red, and green asterisks are related to survival experiments.
Cell survival (solid) and cell membrane permeability (dashed) as a function of the electric field when (A) 50 × 50 HF pulses; (B) 8 × 100 μs pulses; (C) 8 × 5 ms pulses are used. The chosen optimal electric fields are encircled. Each data point presents the mean ± standard deviation from 3–4 experiments. * = statistically significant differences from control (p < 0.05) performing one-way ANOVA if the normality test passed or otherwise ANOVA on ranks. The light blue, red, and green asterisks are related to survival experiments.

FIGURE 4.

Cytotoxicity of cisplatin (A) and cisplatin molecules per cell (B) at different concentrations of cisplatin at a fixed electric field: 1.4 kV/cm for 50 × 50 HF pulses, 1.2 kV/cm for 8 × 100 μs pulses and 0.6 kV/cm for 8 × 5 ms pulses. Each data point presents the mean ± standard deviation from 3–4 experiments. *= statistically significant differences from control (p < 0.05) performing twoway ANOVA test. The color of the asterisk corresponds to the line color for a specific type of tested pulse. Cell survival as a function of cisplatin molecules per cell in combination with electroporation (C) our experimental data and (D) experimental data replotted from Vižintin et al.52 with permission.
Cytotoxicity of cisplatin (A) and cisplatin molecules per cell (B) at different concentrations of cisplatin at a fixed electric field: 1.4 kV/cm for 50 × 50 HF pulses, 1.2 kV/cm for 8 × 100 μs pulses and 0.6 kV/cm for 8 × 5 ms pulses. Each data point presents the mean ± standard deviation from 3–4 experiments. *= statistically significant differences from control (p < 0.05) performing twoway ANOVA test. The color of the asterisk corresponds to the line color for a specific type of tested pulse. Cell survival as a function of cisplatin molecules per cell in combination with electroporation (C) our experimental data and (D) experimental data replotted from Vižintin et al.52 with permission.

FIGURE 5.

Comparison between the number of cisplatin molecules obtained experimentally (asterisks) and using the model (solid line) for (A) 50 × 50 HF pulses, (B) 8 × 100 μs pulses, (C) 8 × 5 ms pulses, (D) 1 × 200 ns pulses, and (E) 25 × 400 ns pulses. We used three different extracellular concentrations of cisplatin: 0 μM, 10 μM, 30 μM, and 50 μM.
Comparison between the number of cisplatin molecules obtained experimentally (asterisks) and using the model (solid line) for (A) 50 × 50 HF pulses, (B) 8 × 100 μs pulses, (C) 8 × 5 ms pulses, (D) 1 × 200 ns pulses, and (E) 25 × 400 ns pulses. We used three different extracellular concentrations of cisplatin: 0 μM, 10 μM, 30 μM, and 50 μM.

Model parameters

ParameterSymbolValueReference
Electroporation threshold voltageU0258 mV56
Membrane thicknessh5 nm56
Cell radiusr7.5 μm56
Membrane time constantτRC1 µs56
Membrane permittivityɛm12 × 8.85 × 10−12 F/m56
Solute radiusρs0.58 nm58
Defect radiusρd0.8 nm56
Solute radius/Defect radiusλm = ρs/ρd0.725056
Solute diffusivityD1.670 × 10−9 m2/s58,59
Parameter in N formation rateα2 × 10−656
N relaxation rateβ4 × 10−856
Relative permeabilzed conductanceγ1 × 10656
Parameter in M formation rateδ1 × 10−356
M relaxation rateη4 × 10−956
Permeability coefficientξ8.45 × 10−456
Electroporation medium conductivityσ1.4 S/m*
DOI: https://doi.org/10.2478/raon-2024-0005 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
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Language: English
Page range: 51 - 66
Submitted on: Nov 20, 2023
Accepted on: Dec 5, 2023
Published on: Feb 21, 2024
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 times per year
Keywords:
electrochemotherapy,
electroporation,
cisplatin uptake,
phenomenological model,
equivalent pulse parameters
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Haematology, oncology,
Radiology

© 2024 Maria Scuderi, Janja Dermol-Cerne, Janez Scancar, Stefan Markovic, Lea Rems, Damijan Miklavcic, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

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