Irreversible electroporation, electrochemotherapy, and other electroporation-based therapies represent a treatment paradigm for difficult-to-treat solid tumors; the potent combination of high-volta... This review summarizes the use of high-voltage electrical pulses (HVEPs) in clinical oncology to treat solid tumors with irreversible electroporation (IRE) and electrochemotherapy (ECT). HVEPs incr...

Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell–cell and cell–substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies.

Pulsed electric fields interact with the blood–brain barrier (BBB) and have been shown to increase the BBB permeability under some pulsing regimes. Pulsed electric fields may enhance drug delivery to the brain by disrupting the integrity of the BBB and allowing otherwise impermeable drugs to reach target areas. Microfluidic, in vitro models offer an alternative platform for exploring the impact of pulsed electric fields on the BBB because they create physiologically relevant microenvironments and eliminate the confounding variables of animal studies. We developed a microfluidic platform for real-time measurement of BBB permeability pre- and post-treatment with pulsed electric fields. Permeability is measured optically by the diffusion of fluorescent tracers across a monolayer of human cerebral microcapillary endothelial cells (hCMECs) cultured on a permeable membrane. We found that this device is able to capture real-time permeability of hCMEC monolayers for both reversible and irreversible electroporation pulsing regimes. Furthermore, preliminary testing of deep brain stimulation pulsing regimes reveals possible impacts on BBB integrity. This device will enable future studies of pulsed electric field regimes for improved understanding of BBB permeabilization.

Studies have demonstrated that cancer cells tend to have reduced stiffness (Young's modulus) compared to their healthy counterparts. The mechanical properties of primary brain cancer cells, however, have remained largely unstudied. To investigate whether the stiffness of primary brain cancer cells decreases as malignancy increases, we used a microfluidic constriction channel device to deform healthy astrocytes and astrocytoma cells of grade II, III, and IV and measured the entry time, transit time, and elongation. Calculating cell stiffness directly from the experimental measurements is not possible. To overcome this challenge, finite element simulations of the cell entry into the constriction channel were used to train a neural network to calculate the stiffness of the analyzed cells based on their experimentally measured diameter, entry time, and elongation in the channel. Our study provides the first calculation of stiffness for grades II and III astrocytoma and is the first to apply a neural network analysis to determine cell mechanical properties from a constriction channel device. Our results suggest that the stiffness of astrocytoma cells is not well-correlated with the cell grade. Furthermore, while other non-central-nervous-system cell types typically show reduced stiffness of malignant cells, we found that most astrocytoma cell lines had increased stiffness compared to healthy astrocytes, with lower-grade astrocytoma having higher stiffness values than grade IV glioblastoma. Differences in nucleus-to-cytoplasm ratio only partly explain differences in stiffness values. Although our study does have limitations, our results do not show a strong correlation of stiffness with cell grade, suggesting that other factors may play important roles in determining the invasive capability of astrocytoma. Future studies are warranted to further elucidate the mechanical properties of astrocytoma across various pathological grades.