An appealing strategy that overcomes the hydrophobicity of pristine graphene and favors its interaction with biological media is colloidal stabilization in aqueous medium with the support of a biomolecule, such as flavin mononucleotide (FMN), as exfoliating/dispersing agent. However, to establish FMN-stabilized graphene (PG-FMN) as suitable for use in biomedicine, its biocompatibility must be proved by a complete assessment of cytotoxicity at the cellular level. Furthermore, if PG-FMN is to be proposed as a theranostic agent, such a study should include both healthy and tumoral cells and its outcome should reveal the nanomaterial as selectively toxic to the latter. Here, we provide an in-depth comparative in vitro analysis of the response of Saos-2 human sarcoma osteoblasts (model tumor cells) and MC3T3-E1 murine preosteoblasts (undifferentiated healthy cells) upon incubation with different concentrations (10-50 μg mL-1) of PG-FMN dispersions constituted by flakes with different average lateral size (90 and 270 nm). Specifically, the impact of PG-FMN on the viability and cell proliferation, reactive oxygen species (ROS) production, and the cellular incorporation process, cell-cycle progression, and apoptosis has been evaluated. PG-FMN was found to be toxic to both types of cells by increasing ROS production and triggering cell-cycle arrest. The present results constitute a cautionary tale on the need to establish the effect of a nanomaterial not only on tumor cells but also on healthy ones before proposing it as anticancer agent.
Keywords: ROS; flavin mononucleotide; in vitro cell response; osteoblasts; pristine graphene.