Reduced graphene oxide: nanotoxicological profile in rats

Abstract

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.

Silver-doped graphene oxide nanocomposite triggers cytotoxicity and apoptosis in human hepatic normal and carcinoma cells

“…The large size of rGO hinders drug delivery in the bloodstream. Mendonça et al 28 reported that small-size graphene oxide is easily phagocytosed and more applicable for drug loading. In this study, we used rGo-Ag nanocomposite.…”

PEGylation of Reduced Graphene Oxide Induces Toxicity in Cells of the Blood–Brain Barrier: Anin Vitroandin VivoStudy

“…The in vitro concentration of rGO-PEG (100 µg/ml) was selected as a function of the concentration already used for in vivo experiments (7 mg/kg) [10,11]. For the calculation, we considered a 200 g rat with blood volume average of 14 ml [15].…”

“…We have previously demonstrated that water-suspended rGO injected in rats through the tail vein (i.v.) induces a transient disruption of the paracellular tightness of the blood-brain barrier (BBB) in the hippocampus [10], with a relatively low toxicity for the vital organs [11]. The BBB is a dynamic interface that separates the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 4 peripheral circulating blood and the CNS microenvironment.…”

Targeted imaging and induction of apoptosis of drug-resistant hepatoma cells by miR-122-loaded graphene-InP nanocompounds

“…If the graphene oxide sizes are too large, drug delivery in the blood stream would be affected. Whereas if graphene oxide sizes are too small, drug loading would be affected, and particle phagocytosis would readily occur [23]. Thus, in the present study, we concluded that the size of graphene oxide should be approximately 300 nm (achieved through gradient centrifugation) to ensure its drug loading and to avoid phagocytosis by phagocytic cells in vivo.…”