Comparative physicochemical study of dielectric barrier discharge and post-discharge plasmas to treat non-small cell lung carcinoma in murine models

Abstract While cold atmospheric plasmas (CAPs) are increasingly explored for cancer therapy, it remains unclear how distinct device configurations translate into differences in tissue coupling, safety, and therapeutic efficacy. To address this gap, a comparative evaluation of the two following CAP sources has been conducted: the ORJET (atmospheric pressure plasma jet in outer ring electrode configuration) and the PoDBD (post-discharge delivered by a dielectric barrier device with a grounded-mesh electrode). Electrical behavior is quantified on an equivalent electrical human body model, while optical emission spectroscopy and surface-oxidation assays are achieved on transdermal membranes and polyethylene substrates to characterize the nature and diffusion of plasma-generated reactive species. Thermal safety is examined in mice through real-time temperature monitoring and histological analysis while antitumor efficacy is determined in a syngeneic model of non-small cell lung cancer (NSCLC) treated five times. The two devices display fundamentally different modes of tissue coupling: ORJET delivers localized interfacial electric field while PoDBD exposes tissue solely to reactive oxygen and nitrogen species-rich post-discharge. Despite these differences, both generate similar reactive-species signatures, preserve tissue integrity when operated within safe thermal limits, and significantly slow tumor progression compared with controls, with no difference between devices. These findings indicate that therapeutic activity arises predominantly from reactive-species chemistry rather than electrical coupling, supporting the applicability of diverse CAP technologies for oncological treatment.