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

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 nonoxidized 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.     

Mechanistic Insight into Permeation of Plasma-Generated Species from Vacuum into Water Bulk

Due to their potential benefits, cold atmospheric plasmas (CAPs), as biotechnological tools, have been used for various purposes, especially in medical and agricultural applications. The main effect of CAP is associated with reactive oxygen and nitrogen species (RONS). In order to deliver these RONS to the target, direct or indirect treatment approaches have been employed. The indirect method is put into practice via plasma-activated water (PAW). Despite many studies being available in the field, the permeation mechanisms of RONS into water at the molecular level still remain elusive. Here, we performed molecular dynamics simulations to study the permeation of RONS from vacuum into the water interface and bulk. The calculated free energy profiles unravel the most favourable accumulation positions of RONS. Our results, therefore, provide fundamental insights into PAW and RONS chemistry to increase the efficiency of PAW in biological applications.