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

Author:

Berner Julia12,Miebach Lea13ORCID,Herold Luise12,Höft Hans4,Gerling Torsten15ORCID,Mattern Philipp15,Bekeschus Sander1ORCID

Affiliation:

1. ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Straße 2, 17489 Greifswald, Germany

2. Department of Oral, Maxillofacial and Plastic Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany

3. Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany

4. Department of Plasma Diagnostics, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Straße 2, 17489 Greifswald, Germany

5. Diabetes Competence Centre Karlsburg (KDK), Leibniz Institute for Plasma Science and Technology (INP), Greifswalder Straße 11, 17495 Karlsburg, Germany

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.

Funder

Federal Ministry of Education and Research

Ministry of Economics, Employment and Health of the state Mecklenburg-Vorpommern

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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