THE CANCER BURDEN : WILL GRAPHENE BE ABLE TO TAKE ITS LOAD? FAREEHA ARSHAD M.Sc. (2019) Aligarh Muslim University, Uttar Pradesh , 202002
Quantification of Cancer Biomarkers Using Graphene-Based Biosensors
Abstract The recent years have witnessed great developments in the area of graphene-based nanomaterials having potential application in cancer diagnostics. Graphene-based biosensors make the process of cancer biomarker diagnosis more sensitive, specific, and selective. Because of their synergistic properties, they essentially have both imaging and therapeutic properties.
Many works reported new ideas for creating sandwich-type graphene-based electrochemical immunosensors for detection of Carcino Embryonic Antigens (CEA) biomarkers. Most suggest using graphene as a biosensing platform at the electrode surface and as a label agent to increase sensitivity.
I searched the PubMed database for review and research papers published between 2010 and 2020, using the keywords “graphene” + “biosensors” + “cancer biomarkers” + “graphene sensors” and observed that the current scientific aim is to create a smaller and portable point of care devices for easy and early cancer detection. There are many researches done in the fabrication of recognition units enabling graphene including aptamers, enzymes, and antibodies for specific cancer identification. However, there are still researches need to be carried out for optimization of these sensors to be made available for real-world clinical applications. Also, the bio-safety of graphene and its derivatives especially about graphene’s monitoring and control of their metabolic pathways, their cellular uptake mechanisms, and long-term toxicity has to be studied. More importantly, additional research needs to be to create more scalable, reproducible, and reproducible methods for the synthesis of graphene-based nanomaterial. The graphene-based biosensors are promising entities for serving early and optimal cancer diagnostics by detecting different cancer biomarkers within the samples simultaneously. Designing easier, faster and smaller graphene-based biosensors will increase the potential application of graphene in early cancer diagnostics.
Introduction Cancer Despite the innumerable research and progresses made in the last decade, cancer is still one of the leading causes of death worldwide[1]. Once diagnosed, the cancer patients undergo stage determination by bio imaging or biopsy, followed by chemo or radiation therapy, and/or surgery – which are painful procedures and break patient both physically, mentally and emotionally.
[1] GBD 2015 Mortality and Causes of Death Collaborators. “Global, regional, and national life expectancy, all-cause mortality, and causespecific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.” Lancet (London, England) vol. 388,10053 (2016): 1459-1544. doi:10.1016/S01406736(16)31012-1
The members of the graphene family materials: few-layered graphene (a), graphene nanosheet (b), graphene oxide (c), and reduced graphene (d) Jastrzębska, Agnieszka Maria et al. “Recent advances in graphene family materials toxicity investigations.” Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology vol. 14,12 (2012): 1320. doi:10.1007/s11051-0121320-8
Graphene
Biosensors
Graphene is an aromatic, hydrophobic, and a chemically inert molecule making it biocompatible. Due to the π- π interactions between its hexagonal cells and carbon rings of biomolecules, graphene can adsorb the biomolecules[2]. Additionally, because of graphene’s two-dimensional nanostructure, no geometric constraints are visible as observed in other carbon-based devices. Its oxidative form, graphene oxide (GO), is highly versatile. The presence of the oxygen groups on GO makes it highly functional and helps in preparation of nanocomposites.
Biosensors are powerful analytical devices that recognize and detect different biomolecules with high specificity, selectivity, and sensitivity[3]. Among all the sensing devices, electrochemical biosensors have received the most attention for the detection of clinical biomarkers and other analytes. The large specific surface area coupled with the excellent electrical conductivity of graphene and graphene derivatives allow protein adsorption and rapid electron transfer between the redox centres and the surface of the electrode. This allows accurate and selective detection of the target biomolecules[4].
[2] Yang, Guohai et al.. “Graphene-like two-dimensional layered nanomaterials: applications in biosensors and nanomedicine.” Nanoscale vol. 7,34 (2015): 14217-31. doi:10.1039/c5nr03398e
[3] Hunt, Heather K, and Andrea M Armani. “Label-free biological and chemical sensors.” Nanoscale vol. 2,9 (2010): 1544-59. doi:10.1039/c0nr00201a [4] Bai, Yunlong et al.. “Graphene-Based Biosensors for Detection of Biomarkers.” Micromachines vol. 11,1 60. 3 Jan. 2020, doi:10.3390/mi11010060
Protein p53 is a very common and well-known tumour suppressor. Any change or loss in its function due to its conformational changes may result in gene mutations and even tumour formation[6]. The sandwich-type strategy has been employed in the majority of electrochemical graphene-based imunosensors for detection of phosphorylated p53. [6] Bode A.M., Dong Z.G. Post-translational modification of p53 in tumorigenesis. Nat. Rev. Cancer. 2004;4:793–805. doi: 10.1038/nrc1455
The alpha-fetoprotein (AFP) is a fetal component glycoprotein that is produced at the embryonic stage. For developing noble electrochemical immunoassay, the graphenebased materials have been extensively studied for amplifying the detection sensitivity of AFP.
Recent research works suggest that graphene can be used as an effective platform for detection of multiplex cancer tumour biomarkers. Li et al. developed suspended crystalline graphene (SCG) biosensor for detection of multiplex lung cancer biomarkers[7] which had the lowest detection limit to be ever reported for the three tumour biomarkers. [7] Li P., Zhang B., Cui T. Towards intrinsic graphene biosensor: A label-free, suspended single crystalline graphene sensor for multiplex lung cancer tumor markers detection. Biosens. Bioelectron. 2015;72:168–174. doi: 10.1016/j.bios.2015.05.007
Discussion and Conclusion
Though graphene based biosensors have booming advantages, which are encouraging and exciting to experiment with, there are a few challenges that still need our attention especially its clinical practicality. Additionally, a universal and uniform standard has to be set up in order to develop such kinds of graphene-based biosensors that have higher practicality towards cancer biomarker diagnosis. Though graphene-based biosensors have a huge potential, because of its toxicity it poses many health concerns against its usage. Recent studies, however, suggest that the cytotoxicity of graphene and its derivatives depend upon many factors including preparation protocols, purification processes, and final physicochemical properties[5]. In addition, because of cancers’ heterogeneous nature, it is difficult to detect and diagnose a single biomarker that is highly specific and sensitive to the biosensor. Biological samples like blood plasma, blood serum, saliva, urine are a challenge because of the existence of a complex system within them. This issue can be resolved by passivization of the sensor's surface with an anti-fouling agent. Also, repeated filtration and purification techniques can be employed to concentrate the target analyte for better analysis of the target biomarker in the sample. Regardless, researchers are already conquering these shortcomings as we speak. It is indeed impossible to deny the elegant versatility and unmatched properties graphene possess, which in turn makes the process of cancer biomarker diagnosis more reliable. We will soon have such graphene-based devices made clinically available and make the painful process of cancer treatment a lot easier. [5] Gonçalves G., Vila M., Portolés M.-T., Vallet-Regi M., Gracio J., Marques P.A.A.P. Nano-graphene oxide: A potential multifunctional platform for cancer therapy. Adv. Healthc. Mater. 2013;2:1072–1090. doi: 10.1002/adhm.201300023