How Nanomedicine Could Help to Identify COVID-19 and Prevent Deaths
Steven Mufamadi, South Africa
Liam Critchley, United Kingdom
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world shows no signs of stopping. Coronavirus cases continue to soar, with more than 5 million cases globally, and more than 350 000 reported deaths since its discovery in late 2019. To combat an epidemic and/or pandemic from COVID-19 demands immediate measures and tools that could enable early and rapid diagnosis, treatment and vaccination for COVID-19.
Experts say the solutions could lie in nanomedicine for stopping Covid-19 outbreaks by identifying patients at high risk and/or helping those that are battling for their lives in the intensive care unit (ICU). Nanomedicine is the application of nanotechnology in medicine. Nanotechnology deals with the creation and manipulation of the chemical and physical properties of a substance at the atomic and molecular level, or nanoscale (i.e. 1-100nm).
Nanotechnology has already showed several impacts towards the fight against COVID-19 since the discovery of the coronavirus, such include 1) the engineering of nanotechnology-based antiviral disinfectants that are highly effective, and that can increase surface disinfection effect or sanitisation in the public transport, hospitals, schools, supermarkets and homes, and handwash sanitizer, 2) a new generation of face masks that could kill the virus immediately, masks that are reusable, washable, recyclable, and self-sterilised, 3) rapid COVID-19 diagnostics kits and 4) Covid-19 treatment and vaccine, some of them are currently undergoing clinical trials, phase I/II.
Identifying Covid-19 Patients at High risk
One of the challenges in the management of the COVID-19 infection is the ability to identify COVID-19 patients that are at greatest risk of death before any major complications arise. Expert believes nanotechnology may also play a role in that space. At different infection level or viral load or stage of disease such as COVID-19, patients may present change of biological fluid composition. These include urine, saliva, tears and plasma and disease-related protein markers and/or patients may present disease-special biological molecules, biomarkers or proteins that may provide disease-specific information with unique patterns.
A recent study by Prof Morteza Mahmoudi, from the MSU's College of Human Medicine, claimed to have engineered nano-based technologies [i.e., protein corona sensor array and magnetic levitation (MagLev)] that could discriminate COVID-19-infected people who are at high risk of death and/or fatal and nonfatal COVID-19 infection at very early stages. To achieve this, they analysed the composition of the biomolecular corona, or crowns, from COVID-19 patient's biological fluids using MagLev and /or protein corona sensor array approaches. The compositions of the biomolecular corona or crowns are disease-related biomarkers such as human proteins, lipids and other molecules with unique surface characteristics and patterns.
Both the MagLev and protein corona sensor array platforms proved to be highly sensitive, specific, and accurate in identifying COVID-19 infected patients at high risk of death. MagLev optical images were analysed through advanced machine learning techniques, in which the experts claim to be capable to produce a “fingerprint” that can distinguish COVID-19 infected individuals, 1) one who will recover on their own and 2) those at risk of death from further complications. Other advantages of using of these nanotechnologies are that they could less social and economic burden and offer better weapon to fight possible future pandemics.
Helping COVID-19 Patients Battling with Cytokine Storms
Many people have died from COVID-19 so far. Studies have shown that cytokine storms may be one of the fuels of COVID-19 death or COVID-19 patients battling in the ICU. Cytokine storms are common complications of coronaviruses [COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)] and the flu. During cytokine storms, the body starts to attack its own cells. Although the doctors have few tools to help those that are suffering from this hyperinflammatory condition, a recent study between researchers in Brazil and France claimed to have successfully developed an in-vivo nanotechnology solution that is effective for the cytokine storms of COVID-19.
The in-vivo study was conducted in mice, in a typical cytokine storm environment seen with COVID-19 infections. Multi-drug nanoparticles were formulated by adding adenosine to Squalene before being encapsulating in the antioxidant alpha-tocopherol. This nanotechnology approach claimed to have delivered a nanotherapy combination safely to the affected tissues. In addition, the results also showed a decrease in the cytokine receptor tumor necrosis factor alpha (TNF alpha) within a tissue, and a concurrent rise in levels of interleukin-10, in both the lungs and the kidneys. The study showed an effective and safe therapy in just four hours.
Point of Care Diagnostics
Nanotechnology is one area that enables devices to be miniaturised and become portable. While a lot of the testing capabilities focus on taking the samples for a lab to be analysed, there is a growing demand for creating devices which can tell a patient if they have/have had the coronavirus at the time of testing. Such point of care devices could offer a way of rapid testing, both in clinical settings and at country borders, to tell if a person entering that environment is a risk to other people and take appropriate real-time measures―therefore stopping the spread from unknown carriers to large populations in real-time rather than when it is too late.
Nanomaterials are highly effective as a sensing material because they have a large and active surface area that can be functionalised with specific receptors. Moreover, the high electrical conductivity of many nanomaterials provides a rapid and sensitive response upon detection. They have been used in a number of real-time sensing platforms before now, but both academic researchers and the nanotechnology industry are creating point of care devices which use nanomaterial as the sensing element. These devices are being created as either nanosensor devices (many of which are FET-based) or microfluidic-based devices.
There are two main nanomaterial being trialled in this area. The first are gold nanoparticles, and the second is graphene. Gold nanoparticles are used because their surface plasmons (highly oscillating surface electrons which are easily excitable) enhance the sensitivity of the device when relevant biomolecules attach. On the other hand, the large and active surface area of graphene, alongside its unparalleled electrical conductivity, provides a rapid response once a biomolecule has attached to its surface-and because its surface is so active, receptors can be easily functionalised on to it.
This is an area where there is a lot of activity as the ability to analyse in real-time and take appropriate measures could be one of the most effective ways of containing the virus-as the quicker people are diagnosed the virus, the quicker it can be contained. As it stands, gold nanoparticle-based sensing devices are already available and prototypes have been created for the graphene-based devices (both microfluidic and nanosensor based) and there are still many academic studies coming out which use these and other nanomaterials. So, it’s likely that we will start to see more nanomaterial point of care devices being used in the fight against the coronavirus and other viruses.
Overall Outlook
Some of the advantages for using nanotechnology approach in the fight against COVID-19 are that it may help to prevent severe shortages of health care resources, provide a real-time diagnosis of the disease (allowing early actions to take place), and minimise death rates-particularly for those at high risk. Aside from the key areas mentioned here, there are other nanotechnology-based interventions that could help to manage COVID-19 in the future, including personalised medicine for COVID-19 patients with chronic diseases, and the engineering of nanotheranostics to combine diagnostics and therapy in one individual system.
References:
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Mahmoudi M, 2020. “Emerging biomolecular testing to assess the risk of mortality from COVID-19 infection”. Molecular Pharmaceutics, https://dx.doi.org/10.1021/acs.molpharmaceut.0c00371
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Dr Steven Mufamadi is the founder and managing director of Nabio Consulting (Pty) Ltd. He holds a PhD in Pharmaceutics from the University of the Witwatersrand, Johannesburg, South Africa. Dr Mufamadi is a finalist of the 2019/2020 NSTF South 32 Awards in the category: Communication award. He is also a Member of the South African Bureau of Standards (SABS) committee on nanotechnologies and Expert Technical Committee for WG5 of ISO/TC 229 on nanotechnologies.
Liam Critchley is a writer and journalist who specialises in Chemistry and Nanotechnology. He holds a MChem Chemistry with Nanotechnology from the University of Hull, United Kingdom and an MSc in Chemical Engineering from the University of Birmingham, United Kingdom. Liam is also a Member of the Advisory Board for the National Graphene Association (NGA) and Nanotechnology World Association (NWA), as well as member of the Trustee Board for the UK Science charity GlamSci.
