Evaluation of toxicity of functionalized graphene oxide with ginsenoside Rh2, lysine and arginine on blood cancer cells (K562), red blood cells, blood coagulation and cardiovascular tissue: In vitro and in vivo studies

摘要

In this study, blood- and cardio-toxicity of Rh2-treated graphene oxide (GO-Rh2), lysine-treated graphene oxide (GO-Lys), arginine-treated GO (GO-Arg), Rh2-treated GO-Lys (GO-Lys-Rh2) and Rh2-treated GO-Arg (GO-Arg-Rh2) were evaluated. Two concentrations of each nanostructures (200 and 1000 mu g/ml) was injected to rats. After 2 weeks, the effects of agents were evaluated on heart tissue by histopathological assays. Cytotoxicity of all designed nanostructures was investigated on blood cancer cells (K562) by MTT assay. Toxicity of designed nanostructures was also investigated on Red Blood Cells (RBCs), Prothrombin Time (PT) and Partial Thromboplastin Time (PTT). The results demonstrated increase of anticancer activity for GO-Arg-Rh2 and GO-Lys-Rh2 in comparison with free Rh2 and GO. GO, GO-Rh2, GO-Lys, GO-Arg, GO-Lys-Rh2, and GO-Arg-Rh2 had 50% hemolysis at concentrations 250, 360, 420, 435, 500, and 575 mu g/ml, respectively. GO led to RBCs aggregation and morphological change at 5-100 mu g/ml, but other functionalized nanostructures did not show these changes. All nanostructures had slight effect on intrinsic and extrinsic coagulation system, especially on PTT. GO-Arg-Rh2 and GO-Lys-Rh2 had lower effect on blood coagulation system in comparison with other examined nanosystems. Besides, GO-Rh2, GO-Arg-Rh2, and GO-Lys-Rh2 had lowest toxicity on heart tissue than other synthesized nanostructures. Functionalization of GO with Arg, Lys, and especially, Rh2 led to decrease the destruction of heart tissue. So, modified GO with Rh2 and basic amino acids may be a potential and promising strategy to enhance the therapeutic index for GO because of the reduction of side effects on normal cells. (C) 2018 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.