Gas plasma technology mediates deep tissue and anticancer events independently of hydrogen peroxide

Reactive oxygen species (ROS) can be used as anticancer agents. Some technologies, such as medical gas plasmas, generate large amounts and varieties of these mainly short-lived, reactive molecules. However, it is unclear how far reactive species travel in tissues and which types have major or minor roles in exerting effects. Here, we used novel hydrogel model systems, tumor organoids, and murine and human tissue to help unravel the intricate interplay between gas plasma-derived reactive species and target tissue. For the first time, we identified lateral reactive species diffusion and tumor cell killing for the kINPen plasma jet. Intriguingly, catalase did not rescue in ovo organoid cancers from lethal oxidative damage. This attributes short-lived reactive species or other gas plasma components, but not hydrogen peroxide (H₂O₂), significant roles in the mediated effects of exposed tissues. Collectively, the findings enable mechanistic insights and empower gas plasma optimization for anticancer treatments.