This article will discuss the potential of graphene oxide in a range of therapeutic procedures, particularly those surrounding neurodegenerative conditions such as Alzheimer’s.
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One of the driving forces associated with the development of Alzheimer’s is thought to be β-amyloid peptides, which form plaques around nerve cells and cause cell death, ultimately impairing brain function. In a paper by Chen et al. (2023) yeast cells bearing misfolded amyloid peptides, as observed in Alzheimer’s patients, can recover following treatment with graphene oxide nanoflakes.
How can Graphene Oxide Combat Amyloid Plaques?
Alzheimer’s is increasingly observed as the population ages, and currently, around 40 million people worldwide are thought to suffer from it or closely related forms of dementia. β-amyloid peptides accumulating in the brain during Alzheimer’s trigger a range of harmful processes that result in cell death and loss of organ function.
Currently, despite a broad and long history of attempts, no best method of combating Alzheimer’s has yet been developed, though many focus on the removal of amyloid plaques as they develop or the prevention of their initial formation. Two-dimensional graphene oxide has been shown to reduce plaque formation in a number of cell models, now including the yeast cell model utilized by Chen et al., which goes some way towards explaining the effect.
Amyloid aggregates exert their neurotoxic influence by causing metabolic stress to nearby cells, which must dispose of misfolded proteins via the endoplasmic reticulum before they encounter other proteins and further cause plaque aggregation. Alongside this, the mitochondria must work harder to fuel the metabolic processes taking place, promoting oxidative stress.
Graphene oxide is a two-dimensional nanomaterial constructed mainly from a flat plane of hexagonally structured carbon atoms, like graphene, but with the addition of oxygen, including functional groups. The material has a high surface energy and thus can adhere to amyloid plaques, coating them and preventing contact with other proteins. The administered graphene oxide nanoflakes are thought to impart a secondary benefit in that they induce a stress response and draw phagocytotic and other immune cells into the area.
What Other Therapeutic Benefits Does Graphene Oxide Offer?
Graphene oxide is a highly adaptable nanomaterial explored for various therapeutic, diagnostic, and sensing applications. Its surface can be functionalized with probes that interact with biomolecules, altering the innate conductivity of the material. As such, the material could be useful in implantable devices that are customized to the continuous monitoring of relevant biomarkers: oncogenic markers in the case of cancer patients, blood glucose levels in diabetic patients, and so on.
The presence of oxygen-containing functional groups on the graphene oxide surface provides more anchor points for such functionalities to be incorporated into the material, though otherwise, it functionally shares many properties with graphene.
Interestingly, reduced graphene oxide, which has had the oxygen functional groups removed but left some lasting effects of their presence within the conjugate system of the molecule, is a superior photothermal therapy agent to either graphene or graphene oxide.
Within photothermal therapy, lasers excite the material through tissue using visible or near-infrared light, which heats them and causes local apoptosis and necrosis. A temperature rise of only ten degrees or so may be sufficient to denature proteins and cause cell death, though more dramatic temperature changes have been achieved.
Owing to the particularities of the delocalized electron system in reduced graphene oxide absorption of near-infrared light, which is maximally penetrating through biological tissue, is around six times higher than in graphene oxide, even exceeding promising inorganic photothermal therapy agents such as gold or iron oxide nanoparticles.
Like nanoparticles constructed from these materials, the highly customizable surface chemistry of graphene oxide nanomaterials can be functionalized with targeting moieties, such as a protein specific to the overexpressed surface receptor of a particular cancer cell type.
As a two-dimensional material, graphene oxide can also be folded into a spherical shape and functional cargo entrapped within. In an example of potential future personalized medicine, customizable nanomaterials such as graphene oxide could be functionalized on the exterior with targeting molecules that firstly ensure enhanced uptake by diseased cells, subsequently be used as photothermal therapy dose enhancers and simultaneously release therapeutic cargo upon the degradation of the nanocapsule. The negatively charged surface of graphene oxide has also shown capacity as an anti-viral material suitable for incorporation into face masks and other surfaces.
Are There Safety Concerns Surrounding the Use of Graphene Oxide Therapeutics?
Functionalized graphene-like materials are being increasingly explored for biomedical applications, though they may pose a range of toxic side effects associated with bioaccumulation, localized inflammation, and potentially cytotoxic and genotoxic effects, possibly acting as a carcinogen.
Most of these effects are associated with the high degree of graphene surface-biomolecule interactions within the body, which, if encountering proteins, can cause dysfunction. Many of these interactions can be blocked by coating the active surface of the nanomaterial with protective agents that reduce contact with endogenous materials, though in turn, this may then reduce the intended therapeutic effect of the nanomedicine.
Overall, graphene and graphene-like materials are promising theranostic agents likely to play some role in the future of personalized medicine.
References and Further Reading
Murphy, M. P., & Levine, H. (2010). Alzheimer's Disease and the Amyloid-β Peptide. Journal of Alzheimer's Disease, 19(1), pp. 311–323. doi.org/10.3233/jad-2010-1221
Chen, X., et al. (2023). Graphene Oxide Attenuates Toxicity of Amyloid‐β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response. Advanced Functional Materials. doi.org/10.1002/adfm.202304053
Dash, B. S., et al. (2021). Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy. International Journal of Molecular Sciences, 22(6), p. 2989. doi.org/10.3390/ijms22062989
Fukuda, M. et al. (2021). Lethal Interactions of SARS-CoV-2 with Graphene Oxide: Implications for COVID-19 Treatment. ACS, 4(11). doi.org/10.1021/acsanm.1c02446
Ou, L., et al. (2016). Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms. Particle and Fibre Toxicology, 13(1). doi.org/10.1186/s12989-016-0168-y