flexible-organic-electronic-devices-for-pulsed-electric-field-therapy

Flexible Organic Electronic Devices for Pulsed Electric Field Therapy of Glioblastoma

Glioblastoma is difficult to eradicate with standard oncology therapies due to its high degree of invasiveness. Bioelectric treatments based on pulsed ...

The combination of Ca ions and electroporation has gained attention as potential alternative to electrochemotherapy. Ca is an important component of the cell membrane repair system and its presence directly influences the dynamics of the pore cycle after electroporation which can be exploited for cancer therapies. Here, the influence of Ca concentration is investigated on small molecule electrotransfer and release of Calcein from 4T1, MX-1, B16F10, U87 cancer cells after cell exposure to microsecond electric pulses. Moreover, we investigated simultaneous molecule electrotransfer and intracellular calcium ion influx when media was supplemented with different Ca concentrations. Results show that increased concentrations of calcium ions reduce the electrotransfer of small molecules to different lines of cancer cells as well as the release of Calcein. These effects are related with an enhanced membrane repair mechanism. Overall, we show that the efficiency of molecular electrotransfer can be controlled by regulating Ca concentration in the electroporation medium. For the first time, the cause of cancer cell death in vitro from 1 mM CaCl concentrations is related to the irreversible loss of Ca homeostasis after cell electroporation. Our findings provide fundamental insight on the mechanisms of Ca electroporation that might lead to improved therapeutic outcomes.

Ca roles in electroporation-induced changes of cancer cell physiology: From membrane repair to cell death.

Glioblastoma Multiforme is a highly lethal form of brain cancer, resistant to traditional therapeutic approaches and oftentimes hardly resectable. The application of pulsed electric fields (PEF) is gaining prominence as a highly effective approach for combating malignant tumors. However, PEF application at high voltages can generate reactive oxygen species through electrochemical events at electrodes, which can greatly affect intracellular processes and damage healthy cells. Here, we present an in depth study on the cellular impact of coating metal electrodes with an organic polymer PEDOT:PSS. We compared the effect of PEF application through coated and uncoated gold electrodes on the U87 human glioblastoma cell line. The results show that PEF application using PEDOT:PSS-coated electrodes does not induce intracellular ROS generation, even at high voltages, contrary to that observed with uncoated electrodes. PEF delivery with PEDOT:PSS coated electrodes results in minimal cell electroporation and a lower intracellular calcium response than uncoated metal electrodes. The application of the antioxidant MnTBAP allowed us to establish that superoxide generation is partially responsible for the higher intracellular calcium response observed in uncoated metal electrodes. The results demonstrate that PEDOT-coated electrodes allow for PEF application without intracellular ROS generation, with the trade-off being a diminished electroporation efficiency. These electrodes could therefore be useful for PEF application in ROS-sensitive tissues, as well as for disentangling the effect of PEFs on cells from the metabolic impact of electrolytic events arising from the electrode material.

Article	Year
Ca roles in electroporation-induced changes of cancer cell physiology: From membrane repair to cell death. Bioelectrochemistry (Amsterdam, Netherlands)\| PubMed ID: 34425390	2021
PEDOT:PSS coated electrodes reduce intracellular oxidation and cell damage with pulsed electric field application. Bioelectrochemistry (Amsterdam, Netherlands)\| PubMed ID: 35665621	2022

Gerwin Dijk

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