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The WHO estimated the annual mortality from drug-resistant diseases to be approximately 700,000, which could increase to 10 million annually by 2050 (World Health Organization, 2019). This major issue in the health sector reflects great risks for our society that could ultimately lead to extreme poverty.
Commonly aroused due to overdosed or unnecessary prescription of antibiotics, antibacterial-resistant "superbugs" are currently considered to be one of the significant challenges in the field of medicine. To conquer these superbugs, the discovery of innovative antibacterial agents that are suited to cease any pathogen or bacterial infection carries significant importance.
Graphene Meets Nanotechnology
A significant evolution in the field of nanoscience and nanotechnology in recent decades has allowed scientists to explore their leverage in various applications, including medicine.
2D graphene-based nanomaterials, such as graphene oxide (GO) and reduced graphene oxide (rGO), are considered to have required properties as antibacterial agents and have already shown great potential in drug delivery systems (Mei, et al., 2020).
First demonstrated at The University of Manchester by Nobel Prize winner scientists Andre Geim and Konstantin Novoselov, graphene is currently considered to be the strongest material in the world. Besides an extraordinary photocatalytic feature, the material is biocompatible, harder than diamond, stronger than steel but lighter than aluminum. Moreover, the hexagonal arrangement of carbon atoms gives graphene material unique physical and chemical properties that can extend an excellent foundation for the development of next-generation technology in the areas of medicine.
Graphene has a large specific surface area that enhances the antibacterial effect by enabling compatible interactions with bacteria membranes. This works in the material's favor, as a low dose can be used compared to conventional antibiotics, accordingly overcoming the problem of bacterial resistance caused by this element (Mei, et al., 2020).
Antibacterial Mechanism to Kill Superbugs
Antibacterial materials, such as metal ions/oxides, antibiotics, quaternary ammonium compounds, and antimicrobial peptides are used for the treatment of bacterial infections, but they show several issues, highlighting the need for a new set of antibiotics (Kumar, Huo, Zhang, & Liu, 2019).
The antibacterial properties of graphene-based nanomaterials were first demonstrated by Hu et al. (W, et al., 2010), who studied the interaction of GO with Gram-negative bacteria, E. coli and concluded a concentration of 85 μg/mL GO could significantly restrain the growth of the bacteria.
A similar interesting result was achieved by Veerapandian et al. (Veerapandian, Zhang, Krishnamoorthy, & Yun, 2013) with E. coli and Salmonella typhimurium, who compared the antibacterial properties of GO nanosheets and UV-radiated GO nanosheets, and demonstrated that the latter case has higher antibacterial activity due to higher rate of cell disruption.
Graphene-based nanomaterials introduce toxicity mechanisms (Krishnamoorthy, Umasuthan, Mohan, Lee, & Kim, 2012) (Akhavan & Ghaderi) to the bacterial membrane by causing oxidative stress through the production of superoxides (Wu, et al., 2017). They can also physically disrupt cellular strain with sharp edges or cell entrapment that limits bacterial movement (X, et al., 2017).
In 2018, researchers from Chalmers University of Technology, Sweden, have come up with the idea of using graphene-coated implants with spikes that make the surface protective and impossible for bacteria to attach to the surface (Malmstedt, 2018).
Human cells are 25 times larger than a bacterium and only suffer from a tiny scratch during this activity. Another in vivo and in vitro study was carried out on Klebsiella pneumoniae, a bacteria that can infect patients with pre-existing conditions of cystic fibrosis, asthma and emphysema (Wu, et al., 2017). A common graphene-based nanomaterial, GO, was introduced, which contained and stopped the bacterial growth, resulting in a convincing increase of cell survival rate.
The chemical mechanism is usually induced by the widely studied treatment method, photothermal therapy, which requires the excitation of a pulsed laser on graphene-based nanomaterials (Wu, Deokar, Liao, Shih, & Ling, 2013). Near-infrared (NIR) photothermal nano agents are preferred for antibacterial substances due to their deep biological tissue penetration capability and minimal damage to healthy tissues. With the material's unique optical properties, it also can absorb light and release it as heat that eventually kills the bacteria (Berger, 2013).
The Challenges of Graphene-Based Nanomaterials
Despite several advantages and huge progress in the medical field, graphene-based nanomaterials still face some challenges (Kumar, Huo, Zhang, & Liu, 2019). The in-depth knowledge about the bacteria-graphene interaction requires better understanding among other bacteria as the majority of the current investigations are of E. Coli and S. Aureus.
As already seen in research in recent years, the continuous study of graphene-based nanomaterials in the field of antibacterial applications has a promising future. With this, only the superpower of graphene can defeat superbugs, hence helping to save more people and avoiding more expensive healthcare costs.
References and Further Reading
Akhavan, O., & Ghaderi, E. (n.d.). Toxicity of Graphene and Graphene Oxide Nanowalls Against Bacteria. ACS Nano, 4. doi:10.1021/nn101390x.
Berger, M. (2013) Replacing antibiotics with graphene-based photothermal agents. [Online] Nanowerk. Available at: https://www.nanowerk.com/spotlight/spotid=29122.php (Accessed on 18 March 2020).
Krishnamoorthy, K., Umasuthan, N., Mohan, R., Lee, J., & Kim, S.-J. (2012) Investigation of the Antibacterial Activity of Graphene Oxide Nanosheets. Science of Advanced Materials, 4, 1-7. doi: 10.1166/sam.2012.140.
Kumar, P., Huo, P., Zhang, R., & Liu, B. (2019) Antibacterial Properties of Graphene-Based Nanomaterials. Nanomaterials. doi:10.3390/nano9050737.
Malmstedt, M. (2018) Spikes of graphene can kill bacteria on implants. [Online] Chalmers. Available at: https://www.chalmers.se/en/departments/bio/news/Pages/Spikes-of-graphene-can-kill-bacteria-on-implants.aspx (Accessed on 18 March 2020).
Mei, L., Zhu, S., Yin, W., Chen, C., Nie, G., Gu, Z., & Zhao, Y. (2020) Two-dimensional nanomaterials beyond graphene for antibacterial applications: current progress and future perspectives. Theranostics 2020, 10(2). doi:10.7150/thno.39701.
Veerapandian, M., Zhang, L., Krishnamoorthy , K., & Yun, K. (2013). Surface activation of graphene oxide nanosheets by ultraviolet irradiation for highly efficient anti-bacterials. Nanotechology. doi:10.1088/0957-4484/24/39/395706.
W, H., C, P., W , L., M, L., X, L., D, L., . . . C, F. (2010). Graphene-based antibacterial paper. ACS Nano. doi:10.1021/nn101097v.
World Health Organization. (2019, 04 29). New report calls for urgent action to avert antimicrobial resistance crisis. [Online] World Health Organization: https://www.who.int/news-room/detail/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis (Accessed on 18 March 2020).
Wu, M.-C., Deokar, A. R., Liao, J.-H., Shih, P.-Y., & Ling, Y.-C. (2013) Graphene-Based Photothermal Agent for Rapid and Effective Killing of Bacteria. ACS nano. doi:10.1021/nn304782d.
Wu, X., Tan, S., Xing, Y., Pu, Q., Wu, M., & Zhao, J. (2017). Graphene oxide as an efficient antimicrobial nanomaterial for eradicating multi-drug resistant bacteria in vitro and in vivo. Colloids and Surfaces B: Biointerfaces, 1-9. doi:10.1016/j.colsurfb.2017.05.024.
X, W., S, T., Y, X., Q, P., M, W., & JX, Z. (2017). Graphene oxide as an efficient antimicrobial nanomaterial for eradicating multi-drug resistant bacteria in vitro and in vivo. Colloids and Surfaces B: Biointerfaces. doi:10.1016/j.colsurfb.2017.05.024.