Plasma-activated Ringer's Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

Epithelial Ovarian Cancer (EOC) is one of the leading causes of cancer-related deaths among women and is characterized by the diffusion of nodules or plaques from the ovary to the peritoneal surfaces. Conventional therapeutic options cannot eradicate the disease and show low efficacy against resistant tumor subclones. The treatment of liquids via cold atmospheric pressure plasma enables the production of plasma-activated liquids (PALs) containing reactive oxygen and nitrogen species (RONS) with selective anticancer activity. Thus, the delivery of RONS to cancer tissues by intraperitoneal washing with PALs might be an innovative strategy for the treatment of EOC. In this work, plasma-activated Ringer's Lactate solution (PA-RL) was produced by exposing a liquid substrate to a multiwire plasma source. Subsequently, PA-RL dilutions are used for the treatment of EOC, non-cancer and fibroblast cell lines, revealing a selectivity of PA-RL, which induces a significantly higher cytotoxic effect in EOC with respect to non-cancer cells

Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

Epithelial Ovarian Cancer (EOC) is one of the leading causes of cancer-related deaths among women and is characterized by the diffusion of nodules or plaques from the ovary to the peritoneal surfaces. Conventional therapeutic options cannot eradicate the disease and show low efficacy against resistant tumor subclones. The treatment of liquids via cold atmospheric pressure plasma enables the production of plasma-activated liquids (PALs) containing reactive oxygen and nitrogen species (RONS) with selective anticancer activity. Thus, the delivery of RONS to cancer tissues by intraperitoneal washing with PALs might be an innovative strategy for the treatment of EOC. In this work, plasma-activated Ringer’s Lactate solution (PA-RL) was produced by exposing a liquid substrate to a multiwire plasma source. Subsequently, PA-RL dilutions are used for the treatment of EOC, non-cancer and fibroblast cell lines, revealing a selectivity of PA-RL, which induces a significantly higher cytotoxic effect in EOC with respect to non-cancer cells

Development and optimization of techniques and design parameters for the engineering of atmospheric pressure plasma devices for biomedical applications and plasma medicine

In the last decades, the possibility to generate plasma at atmospheric pressure gave rise to a new emerging field called plasma medicine; it deals with the application of cold atmospheric pressure plasmas (CAPs) or plasma-activated solutions on or in the human body for therapeutic effects. Thanks to a blend of synergic biologically active agents and biocompatible temperatures, different CAP sources were successfully employed in many different biomedical applications such as dentistry, dermatology, wound healing, cancer treatment, blood coagulation, etc.… Despite their effectiveness has been verified in the above-mentioned biomedical applications, over the years, researchers throughout the world described numerous CAP sources which are still laboratory devices not optimized for the specific application. In this perspective, the aim of this dissertation was the development and the optimization of techniques and design parameters for the engineering of CAP sources for different biomedical applications and plasma medicine among which cancer treatment, dentistry and bioaerosol decontamination. In the first section, the discharge electrical parameters, the behavior of the plasma streamers and the liquid and the gas phase chemistry of a multiwire device for the treatment of liquids were performed. Moreover, two different plasma-activated liquids were used for the treatment of Epithelial Ovarian Cancer cells and fibroblasts to assess their selectivity. In the second section, in accordance with the most important standard regulations for medical devices, were reported the realization steps of a Plasma Gun device easy to handle and expected to be mounted on a tabletop device that could be used for dental clinical applications. In the third section, in relation to the current COVID-19 pandemic, were reported the first steps for the design, realization, and optimization of a dielectric barrier discharge source suitable for the treatment of different types of bioaerosol

Cold atmospheric pressure plasma treatment to assist the restoration of the apical region of a root canal in endodontic procedures

Purpose In Endodontics, in order to complete a root canal treatment, the use of guttapercha to completely seal the root apex must be coupled with endodontic cements known as sealers to improve the adhesion with dentine, despite their cytotoxicity and solubility. The present study investigates the effect of enhancement of adhesion between these materials and Cold Atmospheric Plasma (CAP)-treated dentine of the apical region of ex-vivo teeth as a first step towards the reduction on the use of cytotoxic materials and the use of CAP in-vivo at a clinical stage. Methods A dielectric barrier discharge (DBD) helium plasma jet was used to treat for 180 sec the shaped root canal dentin. Pushout tests and confocal microscopy analysis have been performed to evaluate the effect of cold plasma treatment in terms of adhesion performances and interaction between filling materials and dentin respectively. Results The pushout test results highlight how a 180 seconds CAP treatment of dentin promotes an enhancement of bonding strength between filling materials and dentine in all investigated cases. In particular, when the dentine is CAP-treated in the apical region, the adhesion performances of guttapercha achieved a relevant increase (~ +200%), revealing how it was able to “self-bond” with the substrate with results comparable with the conventional procedure but without any sealer application, while the conventional (guttapercha+sealer) apical sealing procedure shows an improvement around +50%. Moreover, confocal images qualitatively confirmed the higher spreading and penetration of both guttapercha and sealer into dentinal tubules. The ergonomics of the prototype has been also improved to comply with the dimensions of devices commonly used in the dental field, with a plasma source diameter of 21.5 mm and with a choice of materials to minimise its weight. Conclusion CAP treatment of dentin increases the adhesion performances and paves the way for a sealer-free and safer procedure for apical restoration

Cold Atmospheric Pressure Plasma Treatment Modulates Human Monocytes/Macrophages Responsiveness

Monocytes are involved in innate immune surveillance, establishment and resolution on inflammation, and can polarize versus M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages. The possibility to control and drive immune cells activity through plasma stimulation is therefore attractive. We focused on the effects induced by cold-atmospheric plasma on human primary monocytes and monocyte-derived macrophages. Monocytes resulted more susceptible than monocyte-derived macrophages to the plasma treatment as demonstrated by the increase in reactive oxygen (ROS) production and reduction of viability. Macrophages instead were not induced to produce ROS and presented a stable viability. Analysis of macrophage markers demonstrated a time-dependent decrease of the M1 population and a correspondent increase of M2 monocyte-derived macrophages (MDM). These findings suggest that plasma treatment may drive macrophage polarization towards an anti-inflammatory phenotype