Abstract
As an inexpensive monolayer archetypal member of the carbon family, graphene has triggered a new ‘gold rush’ in nanotechnology for achieving unique properties that were not available in many traditional materials. Owing to these unique features, graphene-related materials are finding new uses in nanomedicine and synthetic biology in addition to their diverse applications in electronics, optoelectronics, photonics and environmental clean-up. The increased production of graphene nanostructures and increased likelihood of exposures to these substances in environmental and occupational settings has raised concerns about adverse health outcomes. In particular, the biological effects of these materials need to be assessed to ensure risk free, sustainable development of graphene for widespread applications. In this work, for the first time, we studied the in vitro and in vivo interactions of a relatively new derivative of graphene, graphene nanopores (GNPs) in mammalian systems, to systematically elucidate the possible mechanism of their toxicity over time. This study showed that GNPs induced early apoptosis in both SKMES-1 and A549 lung cancer cells. However, late apoptosis is only induced at concentrations higher than 250μg/ml, suggesting that, although GNPs at lower concentrations induce upregulation of phosphatidylserine on the cell surface membrane (i.e. early apoptotic event), GNPs do not significantly disintegrate the cell membrane. We also showed that rats intraperitoneally injected with GNPs suffered sub-chronic toxicity in a period of 27 days when tested at single and multiple doses of GNPs (5 and 15mg/kg) as evidenced by blood biochemistry, organo-somatic index, liver and kidney enzymes functions analysis, oxidative stress biomarkers and histological examinations. In sum, our results show that GNPs are likely to have a low bioavailability in SKMES-1 and A549 lung cancer cells and rats. Nevertheless, this must be considered against the context of a wider lack of knowledge regarding the bioavailability, fate and behaviour of this type of new porous framework of graphene in natural systems. Therefore, a more long-term GNPs exposure regime, more relevant to real-life environmental consequences, is needed to fully determine the transport capacities of GNPs in living systems.
Highlights
Graphene has become a ‘superstar’ in nanomedicine with applications to improve diagnostics, therapeutics, and genetic risk factors, owing to its multifaceted properties such as small size, large surface area-to-volume ratio, quantum size effects, and unique physicochemical properties [1,2,3]
The present study investigates the toxic effects of graphene nanopores (GNPs) on lung cancer cells (SKMES-1 and A549) in vitro and in rats in vivo, biochemical, serum enzyme analyses, complete blood count as well as histological analysis have been used in this study
A dose-dependent increase in late apoptotic (Fig. 3C) and necrotic cells (Fig. 3D) was observed in A549 cells, no significant increase in necrosis was observed in the SKMES-1 cell line
Summary
Graphene has become a ‘superstar’ in nanomedicine with applications to improve diagnostics, therapeutics, and genetic risk factors, owing to its multifaceted properties such as small size, large surface area-to-volume ratio, quantum size effects, and unique physicochemical properties [1,2,3]. Matharu et al [15] have reported the effects of graphene nanoplatelet-loaded polymer fibres on microbial growth of two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. One drawback of the use of GNP’s is that very few synthesis techniques are available Techniques such as electron beam irradiation, ion bombardment, doping, templating, chemical etching, chemical vapour deposition and other chemical methods have been utilized for their preparation [9,17,18,19,20]. The drawbacks of these methods are the low production yield and the problems associated with their separation/purification.
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