In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma

Jaworski, Sławomir; Sawosz, Ewa; Kutwin, Marta; Wierzbicki, Mateusz; Hinzmann, Mateusz; Grodzik, Marta; Winnicka, A.; Lipińska, L.; Włodyga, Karolina; Chwalibog, A.

doi:10.2147/ijn.s77591

Cited by 71 publications

(39 citation statements)

References 34 publications

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“…3). These results are in agreement with previous studies showing very weak cytotoxic and anti-proliferative effects of graphene films54 and GO55 in murine NIH-3T3 fibroblasts or U87 and U118 glyoma cells, respectively.…”

Section: Resultssupporting

confidence: 93%

Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes

Pelin

Fusco

León

et al. 2017

Sci Rep

153

136

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Impressive properties make graphene-based materials (GBMs) promising tools for nanoelectronics and biomedicine. However, safety concerns need to be cleared before mass production of GBMs starts. As skin, together with lungs, displays the highest exposure to GBMs, it is of fundamental importance to understand what happens when GBMs get in contact with skin cells. The present study was carried out on HaCaT keratinocytes, an in vitro model of skin toxicity, on which the effects of four GBMs were evaluated: a few layer graphene, prepared by ball-milling treatment (FLG), and three samples of graphene oxide (GOs, a research-grade GO1, and two commercial GOs, GO2 and GO3). Even though no significant effects were observed after 24 h, after 72 h the less oxidized compound (FLG) was the less cytotoxic, inducing mitochondrial and plasma-membrane damages with EC50s of 62.8 μg/mL (WST-8 assay) and 45.5 μg/mL (propidium iodide uptake), respectively. By contrast, the largest and most oxidized compound, GO3, was the most cytotoxic, inducing mitochondrial and plasma-membrane damages with EC50s of 5.4 and 2.9 μg/mL, respectively. These results suggest that only high concentrations and long exposure times to FLG and GOs could impair mitochondrial activity associated with plasma membrane damage, suggesting low cytotoxic effects at the skin level.

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Section: Resultssupporting

confidence: 93%

Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes

Pelin

Fusco

León

et al. 2017

Sci Rep

153

136

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show abstract

“…In human glioblastoma cell lines U87 and U118, GO and rGO decreased cell viability and proliferation, however rGO was more toxic than GO. In rGO-treated U87 tumors the expression of caspase-3 was 96 % higher compared with controls [ 34 ]. Herein, no substantial differences were observed in caspase 3 levels in the hippocampal homogenates between controls and animals treated with rGO.…”

Section: Resultsmentioning

confidence: 99%

Reduced graphene oxide: nanotoxicological profile in rats

et al. 2016

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BackgroundWe have previously demonstrated that reduced graphene oxide (rGO) administered intravenously in rats was detected inside the hippocampus after downregulation of the tight and adherens junction proteins of the blood–brain barrier. While down-regulators of junctional proteins could be useful tools for drug delivery through the paracellular pathway, concerns over toxicity must be investigated before clinical application. Herein, our purpose was to trace whether the rGO inside the hippocampus triggered toxic alterations in this brain region and in target organs (blood, liver and kidney) of rats at various time points (15 min, 1, 3 h and 7 days).ResultsThe assessed rGO-treated rats (7 mg/kg) were clinically indistinguishable from controls at all the time points. Hematological, histopathological (neurons and astrocytes markers), biochemical (nephrotoxicity and hepatotoxicity assessment) and genotoxicological based tests showed that systemic rGO single injection seemed to produce minimal toxicological effects at the time points assessed. Relative to control, the only change was a decrease in the blood urea nitrogen level 3 h post-treatment and increases in superoxide dismutase activity 1 h and 7 days post-treatment. While no alteration in leukocyte parameters was detected between control and rGO-treated animals, time-dependent leukocytosis (rGO-1 h versus rGO-3 h) and leukopenia (rGO-3 h versus rGO-7 days) was observed intra-treated groups. Nevertheless, no inflammatory response was induced in serum and hippocampus at any time.ConclusionsThe toxic effects seemed to be peripheral and transitory in the short-term analysis after systemic administration of rGO. The effects were self-limited and non-significant even at 7 days post-rGO administration.

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“…Jaworski et al . 41 studied the toxicity of both GO and rGO in U87 platelets and U118 glioma cells. These results indicated GO and rGO enter glioma cells and show dose-dependent toxicity.…”

Section: Discussionmentioning

confidence: 99%

Reduced graphene oxide triggered epithelial-mesenchymal transition in A549 cells

Liao

Wang

Huang

et al. 2018

Sci Rep

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Graphene and its derivatives have exhibited wide potential applications in electronics, structural engineering and medicine. However, over utilization and untreated discharge may cause its distribution into environmental as well as biological chain, which raised the concerns of potential health risk as a potential hazard. Accumulating evidence has demonstrated that graphene derivatives induce lung fibrosis in vivo, so overall goal of this study was to explore the molecular mechanisms underlying the pulmonary fibrotic responses of reduced graphene oxide (rGO), using in vitro assays. Epithelial-mesenchymal transition (EMT) has profound effect on development of pulmonary fibrosis. Herein, we evaluated the EMT effect of rGO samples on A549 cells. Firstly, rGO penetrated through the A549 cells membrane into the cytosol by endocytosis and located in late endosome and/or lysosomes observed via transmission electron microscopy (TEM), and were well tolerant by cells. Secondly, rGO promoted the cell migration and invasion capacities at lower doses (below 10 μg/ml), but significantly inhibited the capacities at 20 μg/ml. Moreover, rGO-induced EMT were evidenced by decreased expression of epithelial marker like E-cadherin, β-catenin, Smad4 and increased expression of mesenchymal markers like Vimentin, VEGF-B, TWIST1. Based on our findings, it is supposed that rGO can effectively induce EMT through altering epithelial–mesenchymal transition markers in A549 cells.

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In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma

Cited by 71 publications

References 34 publications

Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes

Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes

Reduced graphene oxide: nanotoxicological profile in rats

Reduced graphene oxide triggered epithelial-mesenchymal transition in A549 cells

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