Selective cytotoxic effects of nitrogen-doped graphene coated mixed iron oxide nanoparticles on HepG2 as a new potential therapeutic approach.

New selective therapeutics are needed for the treatment of hepatocellular carcinoma (HCC), the 7th most common cancer. In this study, we compared the cytotoxic effect induced by the release of pH-dependent iron nanoparticles from nitrogen-doped graphene-coated mixed iron oxide nanoparticles (Fe_xO_y/N-GN) with the cytotoxic effect of nitrogen-doped graphene (N-GN) and commercial graphene nanoflakes (GN) in Hepatoma G2 (HepG2) cells and healthy cells. The cytotoxic effect of nanocomposites (2.5-100 ug/ml) on HepG2 and healthy fibroblast (BJ) cells (12-48 h) was measured by Cell Viability assay, and the half maximal inhibitory concentration (IC₅₀) was calculated. After the shortest (12 h) and longest incubation (48 h) incubation periods in HepG2 cells, IC₅₀ values of Fe_xO_y/N-GN were calculated as 21.95 to 2.11 µg.mL^-1, IC₅₀ values of N-GN were calculated as 39.64 to 26.47 µg.mL^-1 and IC₅₀ values of GN were calculated as 49.94 to 29.94, respectively. After 48 h, Fe_xO_y/N-GN showed a selectivity index (SI) of 10.80 for HepG2/BJ cells, exceeding the SI of N-GN (1.27) by about 8.5-fold. The high cytotoxicity of FexOy/N-GN was caused by the fact that liver cancer cells have many transferrin receptors and time-dependent pH changes in their microenvironment increase iron release. This indicates the potential of Fe_xO_y/N-GN as a new selective therapeutic.