Nonthermal treatment with cold atmospheric plasma (CAP) is a promising option for local treatment of chronic-inflammatory and precancerous lesions as well as various mucosal cancer diseases, besides its primary indication for wound healing and antiseptics. Atmospheric pressure plasma jets (APPJs) are versatile plasma sources, some of which are well-characterized and medically approved. The characterization of APPJs, however, is often based on the treatment of simple solutions or even studies on the plasma effluent itself. To better assess the in vivo effects of CAP treatment, this study aims to recapitulate and study the physicochemical tissue-level effects of APPJ treatment on human primary mucosal tissue and tissue models. High resolution on-tissue infrared (IR) thermography and a first-time-performed spatially resolved optical emission spectroscopy (OES) of the APPJ emissions did not identify potentially tissue-harming effects. In this study, electron-spinresonance (ESR) spectroscopy on human tissue samples, treated with different CAP doses, enabled the measurement and the distribution of CAP-derived radicals in the tissues. The results correlate plasma dosage and the generation of radical species with cell viability and cell proliferation of primary human fibroblasts while demonstrating apoptosis-independent antiproliferative cell effects. Moreover, a dose-dependent increase of cells in the G1 phase of the cell cycle was observed, stressing the likely important role of cell cycle regulation for antiproliferative CAP mechanisms. This study introduces suitable methods for CAP monitoring on tissues and contributes to a better understanding of tissue-derived plasma effects of APPJs.

Non‐thermal plasma treatment is one of the promising options for local anti‐neoplastic treatment of dysplastic lesions and early intraepithelial cancer. Primarily, the antiproliferative properties are driven through the generation of reactive oxygen and nitrogen species. In this study, we investigated the amount and distribution of reactive species generated by a non‐thermally operated electrosurgical argon plasma source using electron spin resonance (ESR) spectroscopy. During the plasma treatment of both, aqueous solution and solid human preputial tissue an increasing amount of different oxygen‐ and carbon‐centered radicals was detected. However, and most probably due to spin trap degradation by the high energy input and the increase of reactive components in aqueous solution, the ESR signal decreased after treatment times exceeding 10 s.

Cold atmospheric plasma (CAP) treatment is developing as a promising option for local anti-neoplastic treatment of dysplastic lesions and early intraepithelial cancer. Currently, high-frequency electrosurgical argon plasma sources are available and well established for clinical use. In this study, we investigated the effects of treatment with a non-thermally operated electrosurgical argon plasma source, a Martin Argon Plasma Beamer System (MABS), on cell proliferation and metabolism of a tissue panel of human cervical cancer cell lines as well as on non-cancerous primary cells of the cervix uteri. Similar to conventional CAP sources, we were able to show that MABS was capable of causing antiproliferative and cytotoxic effects on cervical squamous cell and adenocarcinoma as well as on non-neoplastic cervical tissue cells due to the generation of reactive species. Notably, neoplastic cells were more sensitive to the MABS treatment, suggesting a promising new and non-invasive application for in vivo treatment of precancerous and cancerous cervical lesions with non-thermally operated electrosurgical argon plasma sources.

No abstract