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Medical Gas Plasma Jet Technology Targets Murine Melanoma in an Immunogenic Fashion
Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune-infiltrates of CD8+ cytotoxic T-cells and dendritic cells. T-cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat-shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.
Microbial Control of Raw and Cold-Smoked Atlantic Salmon (Salmo salar) through a Microwave Plasma Treatment
The control of the pathogenic load on foodstuffs is a key element in food safety. Particularly, seafood such as cold-smoked salmon is threatened by pathogens such as Salmonella sp. or Listeria monocytogenes. Despite strict existing hygiene procedures, the production industry constantly demands novel, reliable methods for microbial decontamination. Against that background, a microwave plasma-based decontamination technique via plasma-processed air (PPA) is presented. Thereby, the samples undergo two treatment steps, a pre-treatment step where PPA is produced when compressed air flows over a plasma torch, and a post-treatment step where the PPA acts on the samples. This publication embraces experiments that compare the total viable count (tvc) of bacteria found on PPA-treated raw (rs) and cold-smoked salmon (css) samples and their references. The tvc over the storage time is evaluated using a logistic growth model that reveals a PPA sensitivity for raw salmon (rs). A shelf-life prolongation of two days is determined. When cold-smoked salmon (css) is PPA-treated, the treatment reveals no further impact. When PPA-treated raw salmon (rs) is compared with PPA-untreated cold-smoked salmon (css), the PPA treatment appears as reliable as the cold-smoking process and retards the growth of cultivable bacteria in the same manner. The experiments are flanked by quality measurements such as color and texture measurements before and after the PPA treatment. Salmon samples, which undergo an overtreatment, solely show light changes such as a whitish surface flocculation. A relatively mild treatment as applied in the storage experiments has no further detected impact on the fish matrix.
Plasma-Treated Solutions (PTS) in Cancer Therapy
Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indi-cated that the PTS has immuno-stimulatory properties. Two different routes of application are cur-rently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection
Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH.
Investigating the Mutagenicity of a Cold Argon-Plasma Jet in an HET-MN Model
Objective: So-called cold physical plasmas for biomedical applications generate reactive oxygen and nitrogen species and the latter can trigger DNA damage at high concentrations. Therefore, the mutagenic risks of a certified atmospheric pressure argon plasma jet (kINPen MED) and its predecessor model (kINPen 09) were assessed. Methods: Inner egg membranes of fertilized chicken eggs received a single treatment with either the kINPen 09 (1.5, 2.0, or 2.5 min) or the kINPen MED (3, 4, 5, or 10 min). After three days of incubation, blood smears (panoptic May-Grünwald-Giemsa stain) were performed, and 1000 erythrocytes per egg were evaluated for the presence of polychromatic and normochromic nuclear staining as well as nuclear aberrations and binucleated cells (hen’s egg test for micronuclei induction, HET-MN). At the same time, the embryo mortality was documented. For each experiment, positive controls (cyclophosphamide and methotrexate) and negative controls (NaCl-solution, argon gas) were included. Additionally, the antioxidant potential of the blood plasma was assessed by ascorbic acid oxidation assay after treatment. Results: For both plasma sources, there was no evidence of genotoxicity, although at the longest plasma exposure time of 10 min the mortality of the embryos exceeded 40%. The antioxidant potential in the egg’s blood plasma was not significantly reduced immediately (p = 0.32) or 1 h (p = 0.19) post exposure to cold plasma. Conclusion: The longest plasma treatment time with the kINPen MED was 5–10 fold above the recommended limit for treatment of chronic wounds in clinics. We did not find mutagenic effects for any plasma treatment time using the either kINPen 09 or kINPen MED. The data provided with the current study seem to confirm the lack of a genotoxic potential suggesting that a veterinary or clinical application of these argon plasma jets does not pose mutagenic risks.
Elucidation of Plasma-induced Chemical Modifications on Glutathione and Glutathione Disulphide
Cold atmospheric pressure plasmas are gaining increased interest in the medical sector and clinical trials to treat skin diseases are underway. Plasmas are capable of producing several reactive oxygen and nitrogen species (RONS). However, there are open questions how plasma-generated RONS interact on a molecular level in a biological environment, e.g. cells or cell components. The redox pair glutathione (GSH) and glutathione disulphide (GSSG) forms the most important redox buffer in organisms responsible for detoxification of intracellular reactive species. We apply Raman spectroscopy, mass spectrometry, and molecular dynamics simulations to identify the time-dependent chemical modifications on GSH and GSSG that are caused by dielectric barrier discharge under ambient conditions. We find GSSG, S-oxidised glutathione species, and S-nitrosoglutathione as oxidation products with the latter two being the final products, while glutathione sulphenic acid, glutathione sulphinic acid, and GSSG are rather reaction intermediates. Experiments using stabilized pH conditions revealed the same main oxidation products as were found in unbuffered solution, indicating that the dominant oxidative or nitrosative reactions are not influenced by acidic pH. For more complex systems these results indicate that too long treatment times can cause difficult-to-handle modifications to the cellular redox buffer which can impair proper cellular function.