Microscopic Mechanistic Study of the Penetration Distributions for Plasma Reactive Oxygen and Nitrogen Species Based on Sialic Acid Targeting on the Cell Membrane Surface

The ability of cold atmospheric plasmas (CAPs) to produce a wide range of active constituents while maintaining a low or even room temperature of the gas has made it a novel research area of great interest. During plasma action, cancer cell membrane surface components are susceptible to oxidative modification by reactive oxygen and nitrogen species (RONS). In this study, the process of oxidative modification of membrane surface components sialic acid by RONS was investigated based on molecular dynamics simulations, and the penetration mechanism of long-lived particles ONOOH and its homolytic products at the membrane-water interface and the effect of appropriate electric field action were studied. The results showed that cancer cells with high sialic acid expression were less stable than healthy cells. Plasma treatment may promote the ONOOH homolysis process, and its homolysis product OH free radical is more likely to adsorb near sialic acid molecules by hydrogen bonding, resulting in oxidative modification. The interaction force between OH free radical and sialic acid molecules is stronger than ONOOH, which helps to further understand the oxidative modification reaction in membrane environment. At the same time, appropriate electric field stimulation can enhance the depth of penetration of RONS to more effectively treat the pathological state of biological tissues. The study proposes the use of membrane surface sialic acid as a cancer therapeutic target and provides guidance for improving the depth of RONS penetration and maximizing the survival of healthy cells, which contributes to the further clinical translation of plasma biomedicine.