scholarly journals Platinum nanoparticles inhibit intracellular ROS generation and protect against cold atmospheric plasma-induced cytotoxicity

Author(s):  
Sebnem Gunes ◽  
Zhonglei He ◽  
David van Acken ◽  
Renee Malone ◽  
Patrick J Cullen ◽  
...  
2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Paras Jawaid ◽  
Mati Ur Rehman ◽  
Qing-Li Zhao ◽  
Masaki Misawa ◽  
Kenji Ishikawa ◽  
...  

Abstract Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• −) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.


2020 ◽  
Vol 15 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Liyun Wang ◽  
Chuankai Xia ◽  
Yajun Guo ◽  
Chunjun Yang ◽  
Cheng Cheng ◽  
...  

Aim: The global of spread multidrug-resistant Pseudomonas aeruginosa has become a public health threat. Cold atmospheric plasma (CAP) is reported to have bactericidal efficacy; however, its effects on clinical super multidrug-resistant P. aeruginosa are unclear. The aim of this study was to investigate the bactericidal efficacy of CAP on a strain of super multidrug-resistant P. aeruginosa. Materials & methods: The effects of CAP treatments were evaluated using assays for the detection of growth, viability, metabolism, virulence factors and reactive oxygen species (ROS) levels. Results: Both CAP treatments dose-dependently inhibited cell viability and metabolic activity, and decreased the expression of several virulence factors. CAP treatment induced a significant increase in intracellular ROS levels, and ROS scavengers inhibited this effect. Conclusion: CAP treatment is a promising option for the clinical inhibition of multidrug-resistant P. aeruginosa, and the development of CAP technologies might be the key to solving the long-standing problem of drug-resistant bacteria.


2019 ◽  
Author(s):  
Zhonglei He ◽  
Kangze Liu ◽  
Laurence Scally ◽  
Eline Manaloto ◽  
Sebnem Gunes ◽  
...  

AbstractCold atmospheric plasma (CAP) has demonstrated synergistic cytotoxic effects with nanoparticles, especially promoting the uptake and accumulation of nanoparticles inside cells. However, the mechanisms driving the effects need to be explored. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP (30 s, 75 kV). CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidated lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrin-dependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. Our data demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake which will be useful for developing more efficient deliveries of nanoparticles and pharmaceuticals into cancer cells for tumour therapy and diagnosis. This mechanism of RONS-induced endocytosis will also be of relevance to other cancer therapies that induce an increase in extracellular RONS.


2021 ◽  
Author(s):  
Sebnem Gunes ◽  
Zhonglei He ◽  
Renee Malone ◽  
Patrick J Cullen ◽  
James F Curtin

AbstractPlatinum nanoparticles (PtNPs) have been investigated for their antioxidant abilities in a range of biological and other applications. The ability to reduce off-target 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 human 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 both cancerous U-251 MG cells and non-cancerous HEK293 cells against CAP induced cytotoxicity. PtNPs may be useful as a catalytic antioxidant for healthy tissue and for protecting against CAP-induced tissue damage.Graphical AbstractPtNPs are potent catalase and superoxide dismutase mimetics which makes them strong antioxidant candidates for the protection of cells against oxidative stress. CAP was generated using a Dielectric Barrier Device (DBD) system with a voltage output of 75 kV at a frequency of 50 Hz. A range of concentrations of 3nm uncoated PtNPs combined with CAP were examined in human U-251 MG Glioblastoma (GBM) cells and non-cancerous human embryonic kidney HEK293 cells. The protective effects of PtNPs against CAP were explored using several biochemical indicators of oxidative stress and cytotoxicity.


2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Xiaorui Yang ◽  
Guodong Chen ◽  
Kwan Ngok Yu ◽  
Miaomiao Yang ◽  
Shengjie Peng ◽  
...  

2018 ◽  
Vol 18 (6) ◽  
pp. 784-804 ◽  
Author(s):  
Georg Bauer

Background: Application of cold atmospheric plasma to medium generates “plasma-activated medium” that induces apoptosis selectively in tumor cells and that has an antitumor effect in vivo. The underlying mechanisms are not well understood. Objective: Elucidation of potential chemical interactions within plasma-activated medium and of reactions of medium components with specific target structures of tumor cells should allow to define the active principle in plasma activated medium. Methods: Established knowledge of intercellular apoptosis-inducing reactive oxygen/nitrogen species-dependent signaling and its control by membrane-associated catalase and SOD was reviewed. Model experiments using extracellular singlet oxygen were analyzed with respect to catalase inactivation and their relevance for the antitumor action of cold atmospheric plasma. Potential interactions of this tumor cell-specific control system with components of plasma-activated medium or its reaction products were discussed within the scope of the reviewed signaling principles. Results: None of the long-lived species found in plasma-activated medium, such as nitrite and H2O2, nor OCl- or .NO seemed to have the potential to interfere with catalase-dependent control of apoptosis-inducing signaling of tumor cells when acting alone. However, the combination of H2O2 and nitrite might generate peroxynitrite. The protonation of peroxnitrite to peroxynitrous acid allows for the generation of hydroxyl radicals that react with H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet oxygen generation and inactivation of membrane-associated catalase through an autoamplificatory mechanism, followed by intercellular apoptosis-inducing signaling. Conclusion: Nitrite and H2O2 in plasma-activated medium establish singlet oxygen-dependent interference selectively with the control system of tumor cells.


2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.


Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 249
Author(s):  
Zhitong Chen ◽  
Richard Obenchain ◽  
Richard E. Wirz

Conventional plasma jets for biomedical applications tend to have several drawbacks, such as high voltages, high gas delivery, large plasma probe volume, and the formation of discharge within the organ. Therefore, it is challenging to employ these jets inside a living organism’s body. Thus, we developed a single-electrode tiny plasma jet and evaluated its use for clinical biomedical applications. We investigated the effect of voltage input and flow rate on the jet length and studied the physical parameters of the plasma jet, including discharge voltage, average gas and subject temperature, and optical emissions via spectroscopy (OES). The interactions between the tiny plasma jet and five subjects (de-ionized (DI) water, metal, cardboard, pork belly, and pork muscle) were studied at distances of 10 mm and 15 mm from the jet nozzle. The results showed that the tiny plasma jet caused no damage or burning of tissues, and the ROS/RNS (reactive oxygen/nitrogen species) intensity increased when the distance was lowered from 15 mm to 10 mm. These initial observations establish the tiny plasma jet device as a potentially useful tool in clinical biomedical applications.


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