Size-dependent genotoxicity of graphene nanoplatelets in human stem cells

Reduced graphene oxide nanoplatelets (rGONPs) were synthesized by sonication of covalently PEGylated GO sheets followed by a chemical reduction using hydrazine and bovine serum albumin. Human mesenchymal stem cells (hMSCs), as a fundamental factor in tissue engineering, were isolated from umbilical cord blood (as a recently proposed source for extracting fresh hMSCs) to investigate, for the first time, the size-dependent cyto- and geno-toxic effects of the rGONPs on the cells. The cell viability test showed significant cell destructions by 1.0 μg/mL rGONPs with average lateral dimensions (ALDs) of 11±4 nm, while the rGO sheets with ALDs of 3.8±0.4 μm could exhibit a significant cytotoxic effect only at highconcentration of 100 μg/mL after 1 h exposure time. Although oxidative stress and cell wall membrane damage were determined as the main mechanism involved in the cytotoxicity of the rGO sheets, neither of them could completely describe the cell destructions induced by the rGONPs, especially at the concentrations ≤ 1.0 μg/mL. In fact, the rGONPs showed genotoxic effects on the stem cells through DNA fragmentations and chromosomal aberrations, even at low concentration of 0.1 μg/mL. Our results present essential knowledge for more efficient and innocuous applications of graphene sheets and particularly nanoplatelets in upcoming nanotechnology-based tissue engineering as, e.g., drug transporter and scaffolds.