Platinum Nanoparticles Inhibit Intracellular ROS Generation and Protect Against Cold Atmospheric Plasma-induced Cytotoxicity

Platinum nanoparticles (PtNPs) have been investigated for their antioxidant abilities in a range of biological and other applications. The ability to reduce off-target cold atmospheric plasma (CAP) cytotoxicity would be useful in Plasma Medicine; however, little has been published to date about the ability of PtNPs to reduce or inhibit the effects of CAP. Here we investigate whether PtNPs can protect against CAP-induced cytotoxicity in cancerous and non-cancerous cell lines. PtNPs were shown to dramatically reduce intracellular reactive species (RONS) production in U-251 MG cells. However, RONS generation was unaffected by PtNPs in medium without cells. PtNPs protect against CAP induced mitochondrial membrane depolarization, but not cell membrane permeabilization which is a CAP-induced RONS-independent event. PtNPs act as potent intracellular scavengers of reactive species and can protect against CAP induced cytotoxicity. PtNPs, showing no significant biocorrosion, may be useful as a catalytic antioxidant for healthy tissue and for protecting against CAP-induced tissue damage

Plasma-activated medium as an innovative anticancer strategy: Insight into its cellular and molecular impact on in vitro leukemia cells

Cold atmospheric plasma (CAP) has received attention as a potential anticancer strategy. In this study, culture medium was exposed to a microsecond-pulsed dielectric barrier discharge jet to produce plasma-activated medium (PAM). On the T-lymphoblastic cell line, PAM induced apoptosis through the activation of the intrinsic pathway and inhibited the cell-cycle progression. The use of the scavengers N-acetylcysteine or O-phenantroline significantly decreased the PAM proapoptotic activity. The genetic impact of PAM on TK6 cells was assessed, resulting in an increased micronuclei frequency. PAM exhibited cytotoxic effects even on leukemia cells cultivated in hypoxia, which plays a critical role in promoting chemoresistance. PAM was also tested on normal lymphocytes, showing its partial selectivity. Taken together, these results contribute to understand the pharmacotoxicological profile of CAP

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

Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the art research in this field, the primary challenges, and future directions to cancer biologists

Non-Thermal Plasma-Induced Immunogenic Cell Death in Cancer: A Topical Review.

Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational benefit of NTP for treatment of cancer relies on its ability to enhance the interactions between NTP-exposed tumor cells and local immune cells which initiates subsequent protective immune responses. This review discusses results from recent investigations of NTP application to induce immunogenic cell death in cancer cells. With further optimization of clinical devices and treatment protocols, NTP can become an essential part of the therapeutic armament against cancer

Low Temperature Plasma for the Treatment of Epithelial Cancer Cells

Biomedical applications of low temperature plasmas (LTP) may lead to a paradigm shift in treating various diseases by conducting fundamental research on the effects of LTP on cells, tissues, organisms (plants, insects, and microorganisms). This is a rapidly growing interdisciplinary research field that involves engineering, physics, life sciences, and chemistry to find novel solutions for urgent medical needs. Effects of different LTP sources have shown the anti-tumor properties of plasma exposure; however, there are still many unknowns about the interaction of plasma with eukaryotic cells which must be elucidated in order to evaluate the practical potential of plasma in cancer treatment. Plasma, the fourth state of matter, is composed of electrons, ions, reactive molecules (radicals and non-radicals), excited species, radiation, and heat. A sufficient dose (time) of plasma exposure can induce death in cancer cells. The plasma pencil is employed to study the anti-tumor properties of this treatment on epithelial cells. The plasma pencil has been previously used for the inactivation of bacteria, destroying amyloid fibrils, and the killing of various cancer cells. Bladder cancer is the 9th leading cause of cancer. In this dissertation, human urinary bladder tissue with the squamous cell carcinoma disease (SCaBER cells) is treated with LTP utilizing two different approaches: direct plasma exposure and Plasma Activated Media (PAM) as an advancement to the treatment. PAM is produced by exposing a liquid cell culture medium to the plasma pencil. Direct LTP treatment of cancer cells indicates a dose-dependent killing effect at post-treatment times. Similarly, PAM treatment shows an anti-cancer effect by inducing substantial cell death. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have an important role in the biomedical effects of LTP treatment. This study demonstrates the capability of the plasma pencil to transport ROS/RNS into cell culture media leading to their activation. The effectiveness of PAM against SCaBER cells is the highest when it is used immediately after preparation. It is found that the killing effect of PAM decreases gradually over time, depending on the dose of plasma exposure. Hydrogen peroxide is known as one of the most stable and impactful ROS in biological systems. Measurements show that the plasma pencil generates a significant amount of hydrogen peroxide in PAM. Interestingly, the concentration of hydrogen peroxide in PAM decreases gradually over time, which correlates well with the decrease of PAM effectiveness with storage time. While the effects of PAM treatment on cancerous epithelial cell lines have been studied, much less is known about the interaction of PAM with normal epithelial cells. Effects of PAM on non-cancerous Madin-Darby Canine kidney (MDCK) epithelial cells indicates that MDCK cells are much more robust than SCaBER cells against PAM treatment. The dose of PAM, which causes a widespread death in SCaBER cells, does not significantly impact viability and morphology of MDCK cells. Time-lapse imaging of normal cells shows that PAM treatment inhibits cell proliferation and random migration. In addition, immunofluorescence staining shows that PAM treatment causes a significant reduction in the nuclear localization of proliferation marker, Ki-67, without any damage to the morphological properties of cells including adhesions and cytoskeleton function. This dissertation clearly demonstrates the capability of PAM treatment in inducing death in cancerous cells that can be important for cancer therapy. Hydrogen peroxide is identified as an important ROS responsible for the anti-tumor properties of PAM, although much additional work remains to comprehensively understand all the involved ROS/RNS and their role in PAM treatment

Sviluppo e caratterizzazione di una sorgente Plasma Gun per applicazioni biomedicali

Cold Atmospheric pressure Plasma (CAP) devices are gaining great interest for their potentials in medical applications, ranging from the inactivation of microbial load to the induction of apoptosis in malignant cells. Therefore, the dissertation was focused on the development of a prototype CAP medical devices, based on Plasma Gun configuration, evaluating its performances in endodontic and oncology fields. Regarding dental applications, a biological investigation of the antibacterial efficacy of Plasma Gun source was carried out on realistic root canal models in collaborations with a group of dental practitioners. Furthermore, the CAP-derived enhancement of adhesion performances of tooth restoration was evaluated along the whole length of ex-vivo root canals. Concerning cancer applications, the CAP-induced apoptosis in Jurkat cells was tested and studied by means of cyto-toxicological analyses. This study represents the first step of a national research project aiming at evaluating the selectively induction of apoptosis in leukemia cell models. Finally, great effort was addressed to the study of optical spectroscopy techniques for the characterization and control of plasma processes: in particular, the poisoning effect of ozone, a molecule extremely relevant for biomedical applications, was investigated through the analysis of O3 and NOx kinetics