Gas Flow Shaping via Novel Modular Nozzle System (MoNoS) Augments kINPen-Mediated Toxicity and Immunogenicity in Tumor Organoids

SIMPLE SUMMARY: Cancer is a devastating disease. New treatment avenues are demanded to promote successful and safe cancer therapies. Gas plasma is a novel tool recently promoted for cancer treatment. This so-called fourth state of matter is known in its hotter forms, such as fire and lightning. Technology leap innovations enabled the usage of gas plasma for medical purposes. In laboratory models, gas plasma has shown promising antitumor effects in several types of cancer. One particularly successful gas plasma device type is called jet plasma. We here attempted to optimize those by testing two adapters mountable on plasma jet devices, which have two functions. One is to increase the amount of ambient air, similar to a turbo coming close to the plasma jet, to produce more free radicals within the same time for anticancer treatment. The second is to add a filter with varying porosity between the plasma jet and the treatment target. This increases the area of free radical deposition, potentially enabling larger skin or tumor treatment areas compared to the focused treatment area of the plasma jet alone. We here provide evidence that such a filter enhanced the antitumor effects of a certified argon plasma jet. ABSTRACT: Medical gas plasma is an experimental technology for anticancer therapy. Here, partial gas ionization yielded reactive oxygen and nitrogen species, placing the technique at the heart of applied redox biomedicine. Especially with the gas plasma jet kINPen, anti-tumor efficacy was demonstrated. This study aimed to examine the potential of using passive flow shaping to enhance the medical benefits of atmospheric plasma jets (APPJ). We used an in-house developed, proprietary Modular Nozzle System (MoNoS; patent-pending) to modify the flow properties of a kINPen. MoNoS increased the nominal plasma jet-derived reactive species deposition area and stabilized the air-plasma ratio within the active plasma zone while shielding it from external flow disturbances or gas impurities. At modest flow rates, dynamic pressure reduction (DPR) adapters did not augment reactive species deposition in liquids or tumor cell killing. However, MoNoS operated at kINPen standard argon fluxes significantly improved cancer organoid growth reduction and increased tumor immunogenicity, as seen by elevated calreticulin and heat-shock protein expression, along with a significantly spurred cytokine secretion profile. Moreover, the safe application of MoNoS gas plasma jet adapters was confirmed by their similar-to-superior safety profiles assessed in the hen’s egg chorioallantoic membrane (HET-CAM) coagulation and scar formation irritation assay.