Conductive Gas Plasma Treatment Augments Tumor Toxicity of Ringer’s Lactate Solutions in a Model of Peritoneal Carcinomatosis

Abstract

Reactive species generated by medical gas plasma technology can be enriched in liquids for use in oncology targeting disseminated malignancies, such as metastatic colorectal cancer. Notwithstanding, reactive species quantities depend on the treatment mode, and we recently showed gas plasma exposure in conductive modes to be superior for cancer tissue treatment. However, evidence is lacking that such a conductive mode also equips gas plasma-treated liquids to confer augmented intraperitoneal anticancer activity. To this end, employing atmospheric pressure argon plasma jet kINPen-treated Ringer’s lactate (oxRilac) in a CT26-model of colorectal peritoneal carcinomatosis, we tested repeated intraabdominal injection of such remotely or conductively oxidized liquid for antitumor control and immunomodulation. Enhanced reactive species formation in conductive mode correlated with reduced tumor burden in vivo, emphasizing the advantage of conduction over the free mode for plasma-conditioned liquids. Interestingly, the infiltration of lymphocytes into the tumors was equally enhanced by both treatments. However, significantly lower levels of interleukin (IL)4 and IL13 and increased levels of IL2 argue for a shift in intratumoral T-helper cell subpopulations correlating with disease control. In conclusion, our data argue for using conductively over remotely prepared plasma-treated liquids for anticancer treatment.

Multi-Oxidant Environment as a Suicidal Inhibitor of Myeloperoxidase

“…Plasma-generated reactive gas phase species are either transported into the liquid or react with molecules and ions present, forming secondary species (Figure 2a). The extent increases when the plasma effluent touches the liquid (conductive mode), as was the case in the current approach [30]. MPO was exposed to plasma in a 96-well plate for different durations (Figure 2b).…”

“…A homemade gas shielding device made of glass [29] (flushed with 3 slm N 2 ) was attached around the jet for the 0.5% oxygen admixture setting, causing a near-laminar curtain gas flow around the jet effluent, suppressing its interaction with the ambient atmosphere. During all treatment conditions, the plasma effluent was in direct contact with the target surface (conducting mode) [30] or at the closest possible distance (when using the shielding device). The evaporated volume was filled up with dH 2 O (or HPLC water), and protein concentration was determined to ensure constant protein concentrations.…”

“…The search engine parameters for PMI-Byonic were set as follows: peptide mass tolerance = 10 ppm, fragment mass tolerance = 10 ppm, cleavage specificity = trypsin, missed cleavages = 2, and total common modifications = 2. A custom modification list was used based on previous experiments [30] (Figure S2). The raw data were filtered using Perseus 2.0.3.0 software and modifications were considered valid if a protein modification occurred in ≥66% replicates of a group.…”

Toxicity and virucidal activity of a neon-driven micro plasma jet on eukaryotic cells and a coronavirus

“…In the interphase, diffusion distances of the plasma gas phase-derived species to target objects such as viruses are minimal, reducing the likelihood of antioxidants to protect such objects by inactivating reactive species. This could also be the reason why stronger effects were seen for the conductive over non-conductive mode because, in the conductive mode, ROS transport from the plasma jet to the liquid is maximized [ 50 , 51 ]. A temperature increase in conductive mode has been described before [ 26 ] and might contribute to ROS-independent effects.…”

Argon Humidification Exacerbates Antimicrobial and Anti-MRSA kINPen Plasma Activity

“…Briefly, the gas plasma jet was installed ( Figure 1 a) on a computer-controlled xyz-stage (CNC step HIGH-Z edition). The distance of the jet to the treated liquid (0 mm, conductive mode [ 25 ]), the jet’s relative position to the well (always: centered), and the exposure time (see legends) were precisely controlled and monitored using appropriate CNC-compatible software. For the addition of oxygen (purity: 4.5; Air Liquide) and nitrogen (purity: 4.5; Air Liquide), a panel of mass flow controllers and valves was used and controlled through a central digital panel (MKS, München, Germany) for sub-percent precision.…”