Cytotoxicity of Nucleotide-Stabilized Graphene Dispersions on Osteosarcoma and Healthy Cells: On the Way to Safe Theranostics Agents

abstract

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 mu g 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

NANOMATERIALS; APOPTOSIS; OXIDE; THERAPEUTICS; GENERATION; PRISTINE; HYBRIDS; STRESS; FLAKES

subject category

Nanoscience & Nanotechnology; Materials Science, Biomaterials

authors

Cicuendez, M; Coimbra, A; Santos, J; Oliveira, H; Ayan-Varela, M; Paredes, UI; Villar-Rodil, S; Vila, M; Silva, VS

Groups

acknowledgements

The characterization of the graphene dispersions by DLS was performed at the ICTS NANBIOSIS by the Nanostructured Liquids Unit (U12) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN), located at the IQAC-CSIC. J. I. P. and S. V.-R. gratefully acknowledge funding by the Spanish Ministerio de Ciencia, Innovacion y Universidades (MICINN), Agencia Estatal de Investigacion (AEI), and the European Regional Development Fund (ERDF) through project RTI2018-100832-B-I00, as well as Plan de Ciencia, Tecnologia e Innovacion (PCTI) 2013-2017 del Principado de Asturias and the ERDF (project IDI/2018/000233). M.C. acknowledges the financial support from the FCT [SFRH/BPD/101468/2014 Postdoctoral Grant]. V.S.S. was funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. FCT, Fundac commaa~o para a Cie<^>ncia e a Tecnologia, I.P., is also acknowledged for the research contract under Scientific Employment Stimulus to H.O. (CEECIND/04050/2017). Thanks are due to CESAM (UIDB/50017/2020+UIDP/50017/2020) for the financial support.