Graphene is a two-dimensional (2D) carbon nanomaterial, which is often referred to as “super material” or “wonder material”. Due to its unique characteristics, graphene is applied in many branches of science and technology, which makes understanding its health risks a critical aspect of its use.
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Graphene is a carbon allotrope with a thickness of a single atom, arranged in a honeycomb-like orientation. To date, the majority of carbon nanomaterials developed are based on graphene. Some of the key advantageous features of graphene are that it can be stacked, rolled, or wrapped to form various structures, such as carbon nanotubes (CNTs), which are used in many industries.
Graphene and Biomedical Applications
As mentioned above, graphene is used in many innovative applications, including nanoelectronics, energy technology that has improved energy storage systems (e.g., highly effective batteries), medical utilities (e.g., antibacterial agents), and the development of composite materials and sensors.
Apart from the aforementioned applications, graphene has been widely applied in biomedical research. For instance, it is used in drug/gene delivery and the development of biocompatible scaffolds for cell culture and biological sensors to detect biomolecules.
Scientists reported that graphene oxide (GO), which is synthesized by fast oxidation of graphite, is an ideal nanocarrier for the efficient delivery of drugs/genes. Gene therapy is a novel approach utilized in the treatment of genetic disorders, such as Parkinson's disease, cystic fibrosis, and cancer.
Owing to the unique properties, such as high specific surface area, superior biocompatibility, enriched oxygen-containing groups, and stability, scientists have been able to load genes/drugs via chemical conjugation or physisorption methods. Recently, researchers have developed polyethyleneimine-modified GO for gene delivery.
Graphene derivatives, e.g., reduced GO (rGO) and doped graphene, have been utilized for the detection of biomolecules, such as amino acids, dopamine, thrombin, and oligonucleotide. GO-based biosensors are also used to identify DNA. Additionally, scientists have used GO for bioimaging of cellular uptake, of polyethylene glycol-modified GO, during drug delivery.
Toxicity of Graphene Nanosheet
Scientists have performed various nanotoxicological studies to determine the risk factors associated with graphene applications and its derivatives. They determined the toxicological profile of graphene nanosheets in both Gram-positive and Gram-negative bacterial models.
These studies have shown that graphene damages bacterial cell membranes via direct contact with the sharp edges of the nanowalls. However, studies have shown that graphene has low toxicity on the luminal macrophages and epithelial cells.
Some of the key determining factors of graphene toxicity to human red blood cells and skin fibroblasts are particulate state, size of the particle, and oxygen content of graphene. Additionally, the functional groups present on the surface of GO nanostructures play a vital role in inducing cytotoxicity.
Genotoxicity and cytotoxicity in human lung fibroblasts associated with GO are due to the generation of reactive oxygen species (ROS) and apoptosis. One of the potential concerns of application GO is that it can induce DNA cleavage, which could lead to many adverse effects on humans.
Graphene and Human Health Risk
Unlike CNTs, minimal research is available regarding the safety of graphene. This is partly due to the initial difficulties associated with enhancing its production. Another reason for the limited knowledge could be that graphene is still in its early developmental stage.
The introduction of carbon nanomaterials in human bodies could result in its accumulation in tissues or elimination via excretion. In the case of accumulation, it could affect the proper functioning of human organs. Additionally, it is important to determine if an individual exposed to graphene induces an immune response or causes inflammation.
One of the major concerns of nanoscopic platelets of graphene-based materials is their thin, lightweight, and tough structure, which causes a detrimental effect when inhaled. Scientists stated that the flakes of carbon might be transported deep inside lung tissues, which might either induce chronic inflammatory responses or inhibit normal cellular functions.
Scientists stated that as the skin is the first interface between the body and the surrounding, it is most exposed to graphene materials. The impact of graphene and GO on the skin depends on their size and physicochemical properties.
Several studies have indicated that exposure to a high concentration of graphene and its derivative for a prolonged period causes membrane damage, indicating low toxicity to skin cells.
Alleviating Graphene-based Nanotoxicity
Several studies have shown that toxicity related to GO can be reduced by altering the surface functional groups and masking the oxygenated functional groups with a biocompatible polymer. For instance, an in vitro study revealed that compared to GO, polyvinylpyrrolidone-modified GO exhibits lower immunogenicity.
Some of the measures undertaken to minimize health risks for workers who are directly associated with the development of graphene or graphene-based technologies include utilizing stable and individual graphene nanosheets that can be easily dispersed in water to reduce aggregation problems in the body.
Other recommendations include using graphene sheets that are small enough to be engulfed by immune cells and readily removed and biodegradable forms of graphene to prevent damages caused by chronic accumulation in tissues.
References and Further Reading
Foley, T. (2021) Graphene Flagship. [Online] Available at: https://graphene-flagship.eu/graphene/news/understanding-the-health-and-safety-of-graphene/
Arvidsson, R., et al. (2018) "Just Carbon": Ideas About Graphene Risks by Graphene Researchers and Innovation Advisors. Nanoethics, 12(3), pp. 199–210. https://doi.org/10.1007/s11569-018-0324-y
Awodele, M.K. et al. (2018) Graphene and its Health Effect Review Article. International Journal of Nanotechnology and Nanomedicine, 3 (2), pp. 1-5.
Seabra, B.A. et al. (2014) Nanotoxicity of Graphene and Graphene Oxide. Chemical Research in Toxicology. 2014, 27, 2. pp.159–168. https://doi.org/10.1021/tx400385x
Bussy, C. et al. (2013) Safety considerations for graphene: lessons learnt from carbon nanotubes. Accounts of Chemical Research, 46(3), pp. 692–701. https://pubs.acs.org/doi/10.1021/ar300199e
Bradley, D. (2012) Is graphene safe? Materials Today, 15 (6), pp. 230. https://doi.org/10.1016/S1369-7021(12)70101-3
Shen, H. et al. (2012) Biomedical applications of graphene. Theranostics, 2(3), pp. 283–294. https://doi.org/10.7150/thno.3642
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