Plasma for cancer treatment: How can RONS penetrate through the cell membrane? Answers from computer modeling

Abstract

Plasma is gaining increasing interest for cancer treatment, but the underlying mechanisms are not yet fully understood. Using computer simulations at the molecular level, we try to gain better insight in how plasma-generated reactive oxygen and nitrogen species (RONS) can penetrate through the cell membrane. Specifically, we compare the permeability of various (hydrophilic and hydrophobic) RONS across both oxidized and non-oxidized cell membranes. We also study pore formation, and how it is hampered by higher concentrations of cholesterol in the cell membrane, and we illustrate the much higher permeability of H₂O₂ through aquaporin channels. Both mechanisms may explain the selective cytotoxic effect of plasma towards cancer cells. Finally, we also discuss the synergistic effect of plasma-induced oxidation and electric fields towards pore formation.

Graphical abstract

Keywords

plasma medicine / cancer treatment / computer modelling / cell membrane / reactive oxygen and nitrogen species

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Acknowledgements

We acknowledge financial support from the Research Foundation−Flanders (FWO; Grant Nos. 1200216N and 11U5416N). The computational work was carried out using the Turing HPC infrastructure at the CalcUA core facility of the Universiteit Antwerpen (UA), a division of the Flemish Supercomputer Center VSC, funded by the Hercules Foundation, the Flemish Government (department EWI) and the UA. We are also very thankful to R. Cordeiro for the very interesting discussions.

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