Understanding the Differences Between Antimicrobial and Cytotoxic Properties of Plasma Activated Liquids

Tsoukou, Evanthia; Bourke, Paula; Boehm, Daniela

doi:10.1615/plasmamed.2018028261

Cited by 23 publications

(29 citation statements)

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“…2c). Comparing with previous results 32 , CAP treatment of culture media for 30 s generated very low amounts of H 2 O 2 (~20 μM), NO 2− (~5 μM), and NO 3− (~30 μM) which are at least 15-fold and 200-fold lower than the IC 50 cytotoxicity values we measured previously for U373MG cells (315 µM, >1200 µM and >600 µM respectively) and therefore are essentially non-toxic 33 www.nature.com/scientificreports www.nature.com/scientificreports/ CAP treatment when measured using H 2 DCFDA by flow cytometry (Fig. 2d).…”

Section: Resultssupporting

confidence: 56%

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis to Repair Oxidised Membrane and Enhance Uptake of Nanomaterial in Glioblastoma Multiforme Cells

Liu

Scally

et al. 2020

Sci Rep

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cold atmospheric plasma (cAp) enhances uptake and accumulation of nanoparticles and promotes synergistic cytotoxicity against cancer cells. However, the mechanisms are not well understood. 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. CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidised lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrindependent 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. We 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. This knowledge will underpin the development of new delivery strategies for theranostic nanoparticles into cancer cells. Cold atmospheric plasma (CAP) is increasingly studied in a growing number of clinical trials for cancer treatment 1,2 and research is ongoing to explore the combination of CAP with other therapies, including nanoparticles, radiotherapy and chemotherapy 3-5. Gold nanoparticles (AuNPs) are known to be weakly-toxic to human cells and be readily manufactured and designed for targeting delivery of various therapeutic compounds into cells. Citrate-capped cationic AuNPs may adsorb serum proteins onto their surface and thereby stimulate receptor-mediated endocytosis 6. Without special surface functionalisation, AuNPs enter cells and become trapped in vesicles 6-8 or enter the nucleus, depending on their size/shape 9,10. Meanwhile, AuNPs with functionalised surface chemistries/ligands can directly penetrate the membrane and enter the cytoplasm 11 .

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Section: Resultssupporting

confidence: 56%

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis to Repair Oxidised Membrane and Enhance Uptake of Nanomaterial in Glioblastoma Multiforme Cells

Liu

Scally

et al. 2020

Sci Rep

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“…As seen in Figure 2c, the RONS generated in CAP-treated phenol red-free medium are presented after normalising to the values of untreated medium. By direct comparison previous results 38 , CAP treatment of culture media for 30 s generated very low amounts of H2O2 (~20 μM), NO 2-(~5 μM), and NO 3-(~30 μM). These concentrations are at least 15-fold and 200-fold lower than the IC50 values we measured previously for U373MG cells (315 µM, >1200 µM and >600 µM respectively) and therefore are essentially non-toxic 39 .…”

Section: Numerical Modelling Of the Uptake Of Aunps By Gbm Cellssupporting

confidence: 61%

“…The generated RONS in the CAP-treated culture medium, including hydrogen peroxide, nitrite and nitrate, were also quantitatively measured (As seen in Figure 2c). By comparison with our previous study 38,42 , after the same low does CAP treatment (30 s, 75 kV), the levels of generated H2O2, NO -2, and NO -3 in culture medium are relatively low cytotoxic to U373MG cells, but still are able to induce lipid peroxidation.…”

Section: Discussionsupporting

confidence: 46%

Low dose Cold Atmospheric Plasma induces membrane oxidation, stimulates endocytosis and enhances uptake of nanomaterials in Glioblastoma multiforme cells

Liu

Scally

et al. 2019

Preprint

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Cold 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.

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“…Baik et al. (2013) and Tsoukou, Bourke, and Boehm (2018) also did not obtain any inactivation or acidification for PBS after plasma treatment. Oehmigen et al.…”

Section: Factors Influencing the Inactivation Efficiency Of Pawmentioning

confidence: 93%

“…The results showed that 5 log reduction of E. coli was achieved after 15 min exposure with PAW, whereas no reduction was observed for PAPBS, and the pH remained 7 after plasma treatment. Baik et al (2013) and Tsoukou, Bourke, and Boehm (2018) also did not obtain any inactivation or acidification for PBS after plasma treatment. Oehmigen et al (2010) investigated the inactivation activity of saline and PBS against E. coli after plasma treatment of 0 to 30 min in three volumes of 1.5, 5.0, and 10.0 mL, and inactivation was observed in nonbuffered solution of all the volumes.…”

Section: Background Environment Of Watermentioning

confidence: 97%

Plasma‐activated water: Physicochemical properties, microbial inactivation mechanisms, factors influencing antimicrobial effectiveness, and applications in the food industry

Zhao

Patange

Sun

et al. 2020

Comp Rev Food Sci Food Safe

201

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Novel nonthermal inactivation technologies have been increasingly popular over the traditional thermal food processing methods due to their capacity in maintaining microbial safety and other quality parameters. Plasma-activated water (PAW) is a cutting-edge technology developed around a decade ago, and it has attracted considerable attention as a potential washing disinfectant. This review aims to offer an overview of the fundamentals and potential applications of PAW in the agri-food sector. A detailed description of the interactions between plasma and water can help to have a better understanding of PAW, hence the physicochemical properties of PAW are discussed. Further, this review elucidates the complex inactivation mechanisms of PAW, including oxidative stress and physical effect. In particular, the influencing factors on inactivation efficacy of PAW, including processing factors, characteristics of microorganisms, and background environment of water are extensively described. Finally, the potential applications of PAW in the food industry, such as surface decontamination for various food products, including fruits and vegetables, meat and seafood, and also the treatment on quality parameters are presented. Apart from decontamination, the applications of PAW for seed germination and plant growth, as well as meat curing are also summarized. In the end, the challenges and limitations of PAW for scale-up implementation, and future research efforts are also discussed. This review demonstrates that PAW has the potential to be successfully used in the food industry.

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Understanding the Differences Between Antimicrobial and Cytotoxic Properties of Plasma Activated Liquids

Abstract: Retention of plasma reactive species to liquids is a promising new technology, an alterna-5-11 and also as a new eco-friendly 12 13 Building an understanding of a

Cited by 23 publications

References 0 publications

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis to Repair Oxidised Membrane and Enhance Uptake of Nanomaterial in Glioblastoma Multiforme Cells

Cold Atmospheric Plasma Stimulates Clathrin-Dependent Endocytosis to Repair Oxidised Membrane and Enhance Uptake of Nanomaterial in Glioblastoma Multiforme Cells

Low dose Cold Atmospheric Plasma induces membrane oxidation, stimulates endocytosis and enhances uptake of nanomaterials in Glioblastoma multiforme cells

Plasma‐activated water: Physicochemical properties, microbial inactivation mechanisms, factors influencing antimicrobial effectiveness, and applications in the food industry

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