Electroporation and cell killing by milli- to nanosecond pulses and avoiding neuromuscular stimulation in cancer ablation

Gudvangen, Emily; Kim, Vitalii; Novickij, Vitalij; Battista, Federico; Pakhomov, Andrei G.

doi:10.1038/s41598-022-04868-x

Cited by 40 publications

(50 citation statements)

References 68 publications

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“…Nanosecond pulses and high-frequency biphasic pulses of a few microsecond duration (H-FIRE) 29 , 30 , 31 were suggested to limit neuromuscular stimulation and contractions. 15 , 16 Additionally, with nanosecond pulses, the possibility of thermal damage to the tissue is minimized 5 , 6 due to low energy being transferred to the treated area and electrochemical reactions are reduced. 8 ECT with nanosecond pulses has shown promising results 8 , 17 , 18 , 19 , but the underlying mechanisms of the observed decrease in cell survival and tumor regression remain to be explained.…”

Section: Discussionmentioning

confidence: 99%

“…7 In addition, nanosecond pulses limit electrochemical reactions at the electrode-electrolyte interface 8 which may affect the treated medium or cells/tissues. [9][10][11] Although a much higher electric field strength is required to achieve a comparable biological effect, excitation thresholds appear to be higher than the electroporation thresholds with nanosecond pulses [12][13][14][15][16] , implying that shortening the pulse duration to nanosecond pulses could also reduce neuromuscular stimulation in electroporation-based applications.…”

Section: Introductionmentioning

confidence: 99%

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Nanosecond electric pulses are equally effective in electrochemotherapy with cisplatin as microsecond pulses

Vižintin

Marković

Ščančar

et al. 2022

Radiology and Oncology

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Background Nanosecond electric pulses showed promising results in electrochemotherapy, but the underlying mechanisms of action are still unexplored. The aim of this work was to correlate cellular cisplatin amount with cell survival of cells electroporated with nanosecond or standardly used 8 × 100 μs pulses and to investigate the effects of electric pulses on cisplatin structure. Materials and methods Chinese hamster ovary CHO and mouse melanoma B16F1 cells were exposed to 1 × 200 ns pulse at 12.6 kV/cm or 25 × 400 ns pulses at 3.9 kV/cm, 10 Hz repetition rate or 8 × 100 μs pulses at 1.1 (CHO) or 0.9 (B16F1) kV/cm, 1 Hz repetition rate at three cisplatin concentrations. Cell survival was determined by the clonogenic assay, cellular platinum was measured by inductively coupled plasma mass spectrometry. Effects on the structure of cisplatin were investigated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Results Nanosecond pulses equivalent to 8 × 100 μs pulses were established in vitro based on membrane permeabilization and cell survival. Equivalent nanosecond pulses were equally efficient in decreasing the cell survival and accumulating cisplatin intracellularly as 8 × 100 μs pulses after electrochemotherapy. The number of intracellular cisplatin molecules strongly correlates with cell survival for B16F1 cells, but less for CHO cells, implying the possible involvement of other mechanisms in electrochemotherapy. The high-voltage electric pulses did not alter the structure of cisplatin. Conclusions Equivalent nanosecond pulses are equally effective in electrochemotherapy as standardly used 8 × 100 μs pulses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanosecond electric pulses are equally effective in electrochemotherapy with cisplatin as microsecond pulses

Vižintin

Marković

Ščančar

et al. 2022

Radiology and Oncology

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“…An Anet A8 3D printer (Shenzhen Anet Technology Co) was modified to serve as an automated arm for accurate placement of a pair of stainless‐steel needle electrodes (0.61 mm diameter, 1.7 mm distance center to center), to facilitate the high‐throughput characterization of the PEF‐induced IRE areas in hESMC and hiPSC‐CM cultures (Casciola et al, 2020; Gudvangen et al, 2022). The heated stage of the 3D printer was used to maintain all wells of the 96‐well plate at 37 ± 1°C.…”

Section: Methodsmentioning

confidence: 99%

“…at different, likely lower, PEF exposures. Furthermore, PEF-induced electrical stimulation and reversible electroporation were also not considered, even though they can be achieved at lower EFTs than cell death (Gudvangen et al, 2022). Future studies are needed to detect PEF effects that were omitted in this tissue-specific focused report.…”

Section: Current Limitations and Future Impactsmentioning

confidence: 99%

Human cardiomyocytes are more susceptible to irreversible electroporation by pulsed electric field than human esophageal cells

Casciola

Keck

Feaster

et al. 2022

Physiological Reports

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Pulse electric field‐based (PEF) ablation is a technique whereby short high‐intensity electric fields inducing irreversible electroporation (IRE) are applied to various tissues. Here, we implemented a standardized in vitro model to compare the effects of biphasic symmetrical pulses (100 pulses, 1–10 μs phase duration (d), 10–1000 Hz pulse repetition rate (f)) using two different human cellular models: human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) and human esophageal smooth muscle cells (hESMCs) cultured in monolayer format. We report the PEF‐induced irreversibly electroporated cell monolayer areas and the corresponding electric field thresholds (EFTs) for both cardiac and esophageal cultures. Our results suggest marked cell type specificity with EFT estimated to be 2–2.5 times lower in hiPSC‐CMs than in hESMCs when subjected to identical PEF treatments (e.g., 0.90 vs 1.85 kV/cm for the treatment of 100 pulses with d = 5 μs, f = 10 Hz, and 0.65 vs 1.67 kV/cm for the treatment of 100 pulses with d = 10 μs, f = 10 Hz). PEF treatment can result in increased temperature around the stimulating electrodes and lead to unanticipated thermal tissue damage that is proportional to the peak temperature rise and to the duration of the PEF‐induced elevated temperatures. In our study, temperature increases ranged from less than 1°C to as high as 30°C, however, all temperature changes were transient and quickly returned to baseline and the highest observed ∆T returned to 50% of its maximum recorded temperature in tens of seconds.

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“…With IRE, an antitumor effect can be achieved without use of any cytotoxic compound or anticancer drug. IRE alone causes dramatic changes in membrane and subsequently cellular homeostasis leading to cell death [ 1 , 3 , 13 ]. Many studies have demonstrated that IRE can be applied in vivo as nonthermal tissue ablation and tumor treatment [ 7 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Ruzgys

Navickaitė

Palepšienė

et al. 2022

Cancers

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Electroporation-based antitumor therapies, including bleomycin electrotransfer, calcium electroporation, and irreversible electroporation, are very effective on directly treated tumors, but have no or low effect on distal nodules. In this study, we aimed to investigate the abscopal effect following calcium electroporation and bleomycin electrotransfer and to find out the effect of the increase of IL-2 serum concentration by muscle transfection. The bystander effect was analyzed in in vitro studies on 4T1tumor cells, while abscopal effect was investigated in an in vivo setting using Balb/c mice bearing 4T1 tumors. ELISA was used to monitor IL-2 serum concentration. We showed that, similarly to cell treatment with bleomycin electrotransfer, the bystander effect occurs also following calcium electroporation and that these effects can be combined. Combination of these treatments also resulted in the enhancement of the abscopal effect in vivo. Since these treatments resulted in an increase of IL-2 serum concentration only in mice bearing one but not two tumors, we increased IL-2 serum concentration by muscle transfection. Although this did not enhance the abscopal effect of combined tumor treatment using calcium electroporation and bleomycin electrotransfer, boosting of IL-2 serum concentration had a significant inhibitory effect on directly treated tumors.

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Electroporation and cell killing by milli- to nanosecond pulses and avoiding neuromuscular stimulation in cancer ablation

Cited by 40 publications

References 68 publications

Nanosecond electric pulses are equally effective in electrochemotherapy with cisplatin as microsecond pulses

Nanosecond electric pulses are equally effective in electrochemotherapy with cisplatin as microsecond pulses

Human cardiomyocytes are more susceptible to irreversible electroporation by pulsed electric field than human esophageal cells

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

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