Biology subjects

Gunes, S.

Publications and source records attributed to Gunes, S..

3 recordsLinked to original sources

bioRxiv2021

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 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/431888v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@128a9f9org.highwire.dtl.DTLVardef@af1f21org.highwire.dtl.DTLVardef@124d6dborg.highwire.dtl.DTLVardef@196040c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2021

Synergistic Cytotoxicity Between Cold Atmospheric Plasma and Pyrazolopyrimidinones Against Glioblastoma Cells

Pyrazolopyrimidinone is a fused nitrogen-containing heterocyclic system, which acts as a core scaffold in many pharmaceutically relevant compounds. Pyrazolopyrimidinones have been demonstrated to be efficient in treating several diseases, including cystic fibrosis, obesity, viral infection and cancer. We have tested the synergistic anti-cancer effects of 15 pyrazolopyrimidinones, synthesised in a two-step process, combined with cold atmospheric plasma (CAP), a novel innovation generating reactive species with other unique chemical and physical effects. We identify two pyrazolopyrimidinones that act as prodrugs and display enhanced reactive-species dependent cytotoxicity when used in combination with cold atmospheric plasma. Synergistic activation was evident for both direct CAP treatment on prodrug loaded tumour cells and indirect CAP treatment of prodrug in media prior to adding to tumour cells. Our results demonstrate the potential of CAP combined with pyrazolopyrimidinones as a programmable cytotoxic therapy against cancer. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/429831v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@56c8aeorg.highwire.dtl.DTLVardef@1913ea9org.highwire.dtl.DTLVardef@a8f522org.highwire.dtl.DTLVardef@75a529_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2019

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

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.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC=\"FIGDIR/small/805192v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@1487fd4org.highwire.dtl.DTLVardef@c05eeforg.highwire.dtl.DTLVardef@198c75aorg.highwire.dtl.DTLVardef@1481096_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗