Models of electroporation and the associated transmembrane molecular transport should be revisited

Scuderi, Maria; Dermol–Černe, Janja; Silva, Clarissa Amaral da; Muralidharan, Aswin; Boukany, Pouyan E.; Rems, Lea

doi:10.1016/j.bioelechem.2022.108216

Cited by 26 publications

(6 citation statements)

References 82 publications

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“…Our previous study demonstrated that existing mechanistic models of electroporation have limited reliability for predicting the transmembrane transport of small molecules across a wide range of pulse parameters. 97 We observed that the contribution of electrophoretic transport during pulse delivery is often overestimated. Therefore, we decided to test a phenomenological model developed by Sweeney et al 56 that neglects electrophoresis and takes into account only diffusion during and after pulse delivery.…”

Section: Discussionmentioning

confidence: 83%

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

Scuderi,

Dermol-Cerne,

Scancar

et al. 2024

Radiology and Oncology

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Background Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipolar pulses has been shown to mitigate pain and muscle contractions. Conversely, the use of millisecond pulses is interesting when combining ECT with gene electrotransfer for the uptake of DNA-encoding proteins that stimulate the immune response with the aim of converting ECT from a local to systemic treatment. Therefore, the aim of this study was to investigate how alternative types of pulses affect the efficiency of the ECT. Materials and methods We performed in vitro experiments, exposing Chinese hamster ovary (CHO) cells to conventional ECT pulses, high-frequency bipolar pulses, and millisecond pulses in the presence of different concentrations of cisplatin. We determined cisplatin uptake by inductively coupled plasma mass spectrometry and cisplatin cytotoxicity by the clonogenic assay. Results We observed that the three tested types of pulses potentiate the uptake and cytotoxicity of cisplatin in an equivalent manner, provided that the electric field is properly adjusted for each pulse type. Furthermore, we quantified that the number of cisplatin molecules, resulting in the eradication of most cells, was 2−7 × 107 per cell. Conclusions High-frequency bipolar pulses and millisecond pulses can potentially be used in ECT to reduce pain and muscle contraction and increase the effect of the immune response in combination with gene electrotransfer, respectively.

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Section: Discussionmentioning

confidence: 83%

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

Scuderi,

Dermol-Cerne,

Scancar

et al. 2024

Radiology and Oncology

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“…The primary transporter responsible for Met uptake is the organic cation transporter (OCT), which is expressed on the cell membrane ( Figure 10 ) [ 88 ]. Prior studies have shown that EP can increase the uptake of external molecules up to 1,000 times (using bleomycin) through transient permeabilization of the cell membrane [ 89 , 90 ] and by increasing the expression of transporters like OCT [ 91 , 92 ]. This suggests a greater drug uptake for the combined treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells

Sahu,

Camarillo,

Sundararajan

2024

Exploration of Targeted Anti-Tumor Therapy

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Aim: Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy. Methods: MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment. Results: Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death. Conclusions: The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.

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“…In comparison to mRNA delivery, efficient delivery of plasmid DNA encoding GFP required approximately double the electric field strength and yielded lower transfection efficiency, viability, and relative yield values. There are likely multiple explanations for the difficulty in delivering plasmid DNA, and the exact transport mechanisms for DNA electrotransfer are not yet well understood 43 , 44 . The relative ease of delivering mRNA is likely influenced by the need for DNA to enter the nucleus for expression and by the relatively small size of our mRNA cargo (~ 1 kB) relative to our plasmid DNA cargo (~ 3.7 kB).…”

Section: Discussionmentioning

confidence: 99%

Scalable continuous-flow electroporation platform enabling T cell transfection for cellular therapy manufacturing

VanderBurgh

Corso

Levy

et al. 2023

Sci Rep

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Viral vectors represent a bottleneck in the manufacturing of cellular therapies. Electroporation has emerged as an approach for non-viral transfection of primary cells, but standard cuvette-based approaches suffer from low throughput, difficult optimization, and incompatibility with large-scale cell manufacturing. Here, we present a novel electroporation platform capable of rapid and reproducible electroporation that can efficiently transfect small volumes of cells for research and process optimization and scale to volumes required for applications in cellular therapy. We demonstrate delivery of plasmid DNA and mRNA to primary human T cells with high efficiency and viability, such as > 95% transfection efficiency for mRNA delivery with < 2% loss of cell viability compared to control cells. We present methods for scaling delivery that achieve an experimental throughput of 256 million cells/min. Finally, we demonstrate a therapeutically relevant modification of primary T cells using CRISPR/Cas9 to knockdown T cell receptor (TCR) expression. This study displays the capabilities of our system to address unmet needs for efficient, non-viral engineering of T cells for cell manufacturing.

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Models of electroporation and the associated transmembrane molecular transport should be revisited

Cited by 26 publications

References 82 publications

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

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

Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells

Scalable continuous-flow electroporation platform enabling T cell transfection for cellular therapy manufacturing

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