Molecular dynamics simulations suggest that the cholesterol-induced stability of lipid membranes during lipid peroxidation offers an explanation for the observed selectivity of plasma treatments towards cancer cells.
We evaluate the anti-cancer capacity of plasma-treated PBS (pPBS), by measuring the concentrations of NO2
− and H2O2 in pPBS, treated with a plasma jet, for different values of gas flow rate, gap and plasma treatment time, as well as the effect of pPBS on cancer cell cytotoxicity, for three different glioblastoma cancer cell lines, at exactly the same plasma treatment conditions. Our experiments reveal that pPBS is cytotoxic for all conditions investigated. A small variation in gap between plasma jet and liquid surface (10 mm vs 15 mm) significantly affects the chemical composition of pPBS and its anti-cancer capacity, attributed to the occurrence of discharges onto the liquid. By correlating the effect of gap, gas flow rate and plasma treatment time on the chemical composition and anti-cancer capacity of pPBS, we may conclude that H2O2 is a more important species for the anti-cancer capacity of pPBS than NO2
−. We also used a 0D model, developed for plasma-liquid interactions, to elucidate the most important mechanisms for the generation of H2O2 and NO2
−. Finally, we found that pPBS might be more suitable for practical applications in a clinical setting than (commonly used) plasma-activated media (PAM), because of its higher stability.
This study is of particular interest for plasma medicine, as plasma generates both ROS and electric fields, but it is also of more general interest for applications where strong electric fields and ROS both come into play.
In recent years, the ability of cold atmospheric pressure plasmas (CAPS) to selectively induce cell death in cancer cells has been widely established. This selectivity has been assigned to the reactive oxygen and nitrogen species (RONS) created in CAPs. To provide new insights in the search for an explanation for the observed selectivity, we calculate the transfer free energy of multiple ROS across membranes containing a varying amount of cholesterol. The cholesterol fraction is investigated as a selectivity parameter because membranes of cancer cells are known to contain lower fractions of cholesterol compared to healthy cells. We find that cholesterol has a significant effect on the permeation of reactive species across a membrane. Indeed, depending on the specific reactive species, an increasing cholesterol fraction can lead to (i) an increase of the transfer free energy barrier height and width, (ii) the formation of a local free energy minimum in the center of the membrane and (iii) the creation of extra free energy barriers due to the bulky sterol rings. In the context of plasma oncology, these observations suggest that the increased ingress of RONS in cancer cells can be explained by the decreased cholesterol fraction of their cell membrane.
In this paper, two types of melanoma and glioblastoma cancer cell lines are treated with cold atmospheric plasma to assess the effect of several parameters on the cell viability. The cell viability decreases with treatment duration and time until analysis in all cell lines with varying sensitivity. The majority of dead cells stains both AnnexinV (AnnV) and propidium iodide, indicating that the plasma‐treated non‐viable cells are mostly late apoptotic or necrotic. Genetic mutations might be involved in the response to plasma. Comparing the effects of two gas mixtures, as well as indirect plasma‐activated medium versus direct treatment, gives different results per cell line. In conclusion, this study confirms the potential of plasma for cancer therapy and emphasizes the influence of experimental parameters on therapeutic outcome.
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