Cold atmospheric plasma, a novel promising anti-cancer treatment modality

Therapeutic effect of cold atmospheric plasma and its combination with radiation as a novel approach on inhibiting cervical cancer cell growth (HeLa cells)

The outlook for the Baltic Sea Region (BSR) health care sector (ScanBalt BioRegion) and the global market situation for MedTech support the introduction of CAP devices. Focus may be to establish an effective BSR trans-national innovation chain within plasma medicine and CAP device development. A snapshot is required of the BSR plasma medicine and CAP device stakeholders. BSR collaboration on plasma medicine and CAP device development should facilitate access to health infrastructures for start-ups and SMEs promoting commercialization based on excellent client validation opportunities, hands-on feedback and input for product development. Regional living labs serving for plasma medicine and CAP device development should be linked together. Commercialization and bringing innovative solutions to hospitals could be assisted by a macro-regional network collaboration. Macro-regional collaboration has the capacity to mobilize regional and national investments and to coordinate those investments with various EU funding sources. Plasma medicine and CAP device development are in the author’s opinion in a position to benefit from macro-regional collaboration. The goal is the Baltic Sea Region as a globally leading hub for plasma medicine research and for CAP edevice development. ScanBalt BioRegion may be a model to be applied for the collaboration.

Cold atmospheric plasma (CAP) attenuates tumor cell proliferation and induces apoptosis in various cell lines. While exerting marginal effects on non-neoplastic cells this unfolds promising applications in cancer therapy. The aim of the study was to analyse the effects of different CAP sources and application times on osteosarcoma (OS) cells and non-malignant fibroblast cell proliferation. U2-OS and 3-T-3 fibroblasts were treated with three different approved medical devices. Carrier gas-treated cells served as controls. Cell proliferation was determined by viable cell count at different time points after treatment. Control exposed U2-OS and 3-T-3 cells exhibited characteristic cell growth. CAP application of U2-OS and 3-T-3 cells attenuated proliferation rates up to 98%. Attenuation rates varied between cell lines, plasma sources and application times. CAP treatment attenuates cell proliferation of OS cancer cells and fibroblasts in a treatment time-dependent manner, whereby U2-OS cells appeared more sensitive to CAP treatment as 3T3 fibroblasts after 10 sec of treatment.

Plasma is the fourth state of matter, and it is species of partially ionized gas generated under an electric field that contains photons, free electrons, ions, free radicals, and reactive oxygen/nitrogen species. Plasma can be produced at atmospheric pressure or under a vacuum in two ways; thermal and non-thermal. Furthermore, they can be classified into natural and artificial plasmas. Non-thermal atmospheric plasma, also known as cold atmospheric plasma (CAP), is produced in a cold form under a high electrical field at atmospheric pressure. CAP is primarily produced using two methods which are the dielectric barrier discharge (DBD) and plasma jet. The electrical discharge between two electrodes separated by an insulating dielectric barrier is known as DBD. This method is quite widely used in many studies in the literature and has an important place in the field of plasma medicine. In the DBD method, the electrode configuration, shape, material, and substance from which the dielectric barrier is made are important. There are many studies conducted with different electrode configurations in the literature. Besides the electrode configuration and shape, the barrier and electrode materials can also affect the reactivity of the discharge by changing the discharge electrical power. It is thought that plasma discharge at different times will vary in CAP applications due to the change in conductivity of the conductive material used depending on the capacitive resistance. In this study, deionized water (DIW) activated with CAP treatment using different electrode materials (copper, stainless steel, and aluminum) to compare the physical quantities that can change such as pH and conductivity. The aim of this study is to observe the effect of using different electrode materials (copper, stainless steel, and aluminum) on the biological outcome of CAP treatment and compare the antimicrobial activities of different materials.

Effects of cold atmospheric plasma therapy on chronic wounds: A systematic review and meta-analysis.

Cold Plasma with Immunomodulatory Properties Has Significant Anti-Lymphoma Activities in Vitro and In Vivo

Plasma medicine is an innovative research field combining plasma physics, life science, and clinical medicine. It is mainly focused on the application cold atmospheric plasma (CAP) in therapeutic settings. Based on its ability to inactivate microorganisms but also to stimulate tissue regeneration, current medical applications are focused on the treatment of wounds and skin diseases. Since CAP is also able to inactivate cancer cells, its use in cancer therapy is expected to be the next field of clinical plasma application. Other promising applications are expected in oral medicine and ophthalmology. It is the current state of knowledge that biological CAP effects are mainly based on the action of reactive oxygen and nitrogen species supported by electrical fields and UV radiation. However, continuing basic research is not only essential to improve, optimize, and enlarge the spectrum of medical CAP applications and their safety, but it is also the basis for identification and definition of a single parameter or set of parameters to monitor and control plasma treatment and its effects. In the field of CAP plasma devices, research and application are currently dominated by two basic types: dielectric barrier discharges and plasma jets. Its individual adaptation to specific medical needs, including its combination with technical units for continuous and real-time monitoring of both plasma performance and the target that is treated, will lead to a new generation of CAP-based therapeutic systems.

Cold atmospheric plasma (CAP) is a novel tool for various applications ranging from hygiene and cosmetics to medicine. In recent years, various CAP devices have been developed for medical applications especially for skin disinfection, blood coagulation, wound healing, and even for cancer treatment. CAPs have bactericidal, fungicidal, virucidal, and sporicidal effects due to the production of reactive species, ultra-violet radiation, electrons, ions, and so on. Therefore, CAPs have the potential for usage in hospital and personal hygiene. CAPs for medical purposes have to be designed individually, e.g. the dose and the plasma properties to eradicate bacteria from cell surfaces are different from the properties used to stop the proliferation of cancer. The CAP devices for medical purposes have to be designed in such a way, so that these are fully compatible with the international safety regulations (especially for the amount of produced reactive species, UV emission, and electrical current). However, the highest efficacy is reached by considering the combination of different CAP components (charged particles, reactive oxygen, and nitrogen species, heat, electric field, and photons), the way of application (direct or indirect with [different distances from the target cell]), the different reaction phenomena in and around the target cell (cell membrane and intracellular biochemistry) along with the defense mechanisms in and around the target cells. Our group has developed a number of different CAP devices using the microwave technology (e.g. MicroPlaSterβ and NanoPlaSter), and the surface micro discharge technology (e.g. HandPlaSter, FlatPlaSter, CylindricalPlaSter, PersonalPlaSter, MiniFlatPlaSter). The strength, weakness, opportunity, and threat analysis show that the technique to use CAP for medical purposes is affordable, simple, easy to handle, and case sensitive – although more studies on the mechanism of the interaction of CAP and cells are necessary. However, the usage of CAPs in ‘medicine – ‘plasma medicine’ – shows a newfangled hope for the development of molecular medicine in the near future possessing an immense market potentiality.

Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.

Cold atmospheric plasma (CAP) is emerging as an innovative approach for cancer treatment because of its selectivity for malignant cells and absence of significant adverse effects. While modern oncological therapies face challenges such as tumor heterogeneity and treatment resistance, CAP presents itself as a low-cost and environmentally sustainable alternative. Its mechanisms of action involve reactive oxygen and nitrogen species (RONS), UV radiation, and electromagnetic fields, which induce cell death. Preclinical and clinical studies have demonstrated the efficacy of CAP, with devices such as dielectric barrier discharge (DBD) and the plasma jet developed to minimize damage to healthy cells. Some CAP devices are already approved for clinical use, showing safety and efficacy. However, the standardization of treatments remains a challenge due to the variety of devices and parameters used. Although CAP has shown promising cytotoxic effects in vitro and in animal models, especially in different cancer cell lines, further research, particularly in vivo and in veterinary medicine, is needed to optimize its clinical use and maximize its efficacy in combating cancer.

Over the past few years, the application of cold atmospheric plasma (CAP) in medicine has developed into an innovative field of research of rapidly growing importance. One promising new medical application of CAP is cancer treatment. Different studies revealed that CAP may potentially affect the cell cycle and cause cell apoptosis or necrosis in tumor cells dependent on the CAP device and doses. In this study, we used a novel hand-held and battery-operated CAP device utilizing the surface micro discharge (SMD) technology for plasma production in air and consequently analysed dose-dependent CAP treatment effects on melanoma cells. After 2 min of CAP treatment, we observed irreversible cell inactivation. Phospho-H2AX immunofluorescence staining and Flow cytometric analysis demonstrated that 2 min of CAP treatment induces DNA damage, promotes induction of Sub-G1 phase and strongly increases apoptosis. Further, protein array technology revealed induction of pro-apoptotic events like p53 and Rad17 phosphorylation of Cytochrome c release and activation of Caspase-3. Interestingly, using lower CAP doses with 1 min of treatment, almost no apoptosis was observed but long-term inhibition of proliferation. H3K9 immunofluorescence, SA-ß-Gal staining and p21 expression revealed that especially these low CAP doses induce senescence in melanoma cells. In summary, we observed differences in induction of apoptosis or senescence of tumor cells in respond to different CAP doses using a new CAP device. The mechanism of senescence with regard to plasma therapy was so far not described previously and is of great importance for therapeutic application of CAP.

Cold Atmospheric Pressure Plasma as a Novel Treatment Modality in Diabetic Foot Ulcers—A Pilot Study

Osteosarcoma (OS) is the most common tumor of the musculoskeletal system. Recently, cold atmospheric plasma (CAP) has been regarded as a promising anti-oncogenic therapy. Previous experimental studies have demonstrated that CAP treatment results in significant growth inhibition of human sarcoma and is able to induce apoptosis. However, due to device-specific parameters, there is a large variability in the antitumor effects of different CAP sources. In the present study, the cellular effects of CAP treatment from two different CAP devices were investigated and their pro-apoptotic efficacy was characterized. The OS cell lines, U2-OS and MNNG/HOS, were treated with two CAP devices, kINPen MED and MiniJet-R. Control groups were treated with argon. The anti-proliferative effect of each treatment was demonstrated using cell counting and the activation of apoptotic mechanisms was determined using Comet, TUNEL and Caspase-3/Caspase-7 assays. The results revealed that treatment of both OS cell lines with the two CAP sources resulted in significant inhibition of cell growth. Subsequently, the activation of Caspases and the induction of apoptotic DNA fragmentation was demonstrated. The biological effects of each CAP source did not differ significantly. The treatment of OS cells with CAP lead to an induction of apoptosis and a reduction of cell growth. Therefore, the biological effects of CAP appear to be general as the two devices of different design produced highly comparable cell responses. Therefore, the type of device used does not seem to affect the efficacy of CAP-based antitumor therapy.

The response of different critical acute and hard-to-heal wounds to an innovative wound care modality-direct application of cold atmospheric plasma (CAP)-was investigated in this clinical case series. Over an observation period of two years, acute wounds with at least one risk factor for chronification, as well as hard-to-heal wounds were treated for 180 seconds three times per week with CAP. CAP treatment was additional to standard wound care. Photographs were taken for wound documentation. The wound sizes before the first CAP treatment, after four weeks, after 12 weeks and at wound closure/end of observation time were determined using image processing software, and analysed longitudinally for the development of wound size. A total of 27 wounds (19 hard-to-heal and eight acute wounds) with a mean wound area of 15cm2 and a mean wound age of 49 months were treated with CAP and analysed. All (100%) of the acute wounds and 68% of the hard-to-heal wounds healed after an average treatment duration of 14.2 weeks. At the end of the observation period, 21% of hard-to-heal wounds were not yet closed but were reduced in size by >80%. In 11% of the hard-to-heal wounds (n=2) therapy failed. The results suggested a beneficial effect of additional CAP therapy on wound healing. This work was carried out within the research projects 'Plasma for Life' (funding reference no. 13FH6I04IA) with financial support from the German Federal Ministry of Education and Research (BMBF). In the past seven years AFS has provided consulting services to Evonik and has received institutional support by Heraeus, Johnson & Johnson and Evonik. There are no royalties to disclose. The Department for Trauma Surgery, Orthopaedics and Plastic Surgery received charitable donations by CINOGY GmbH. CINOGY GmbH released the di_CAP devices and electrodes for the study. WV and AH were involved in the development of the used di_CAP device (Plasmaderm, CINOGY GmbH). WV is shareholder of the outsourced start-up company CINOGY GmbH.

Compact cold atmospheric pressure plasma cleaner suited for inhibiting bacterial biodeteriogens from paper archives