Application Of Nanotechnology In The Treatment Of The Influenza Virus

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Nanotechnology is a revolutionised method that allows for the manipulation of atoms and molecules. Materials at the nanoscale allow for the enhancement of numerous properties such as lighter weight, higher strength, increased control of light spectrum, and greater chemical reactivity. This ability to create resources and devices at the molecular scale allows for immense advancements in the practise and research of medicine. Specifically, these nanomaterials can create electrical super conductivity, which can be used for anti-bacterial properties or binding ability. This can be applied to the prevention and treatment of diseases such as influenza. Influenza is one of the most contagious viral pathogens, affecting millions of people worldwide during seasonal epidemics. In exploring this, the following research question will be investigated, “To what extent does nanomedicine, specifically, the types nanoparticles that assist in the treatment of the influenza virus?”. This will be addressed through the inquisition of the influenza virus and the application of specific nanoparticles to the disease.

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Influenza is a highly contagious viral infection that is transmitted to others through coughing and sneezing. These actions lead to the release of a small virus, allowing contaminated droplets to enter the air, which can then be breathed in and begin to infect the respiratory tract of others. Influenza is a part of the Orthomyxoviridae category, meaning its virus consists of genomes comprised of six to eight segments of single-stranded RNA; this can then be broken down into four genera, Influenzavirus A, B, C, and D. Both influenza A and B viruses are responsible for the widespread seasonal epidemics of the disease, with type A causing the most severe outspreads. This is in comparison to influenza type C, which usually causes a mild respiratory illness. However, unlike all other types, influenza D does not affect humans but instead cattle. Regardless, there are individuals who are at risk of influenza A, B and C related complications these include pregnant women, people aged over 65, Aboriginal and Torres Strait Islander, children younger than the age of 5, people who are obese and people who smoke. Furthermore, symptoms of the disease include a higher fever (38°C or higher), dry cough, body aches (especially in the head, lower back and legs), feeling weak and tired, sore throat, nasal congestion, vomiting and diarrhoea. However, there are treatments that can aid this disease such as resting in bed, taking mild painkillers such as paracetamol, drinking a sufficient amount of liquids (especially water), eating light food and using decongestant medicines. In addition to this, the most effective prevention method of influenza is through vaccinations that allow for the protection of human cells against the pathogen. Consequently, whilst there are somewhat sufficient methods of treating and preventing influenza, the application of nanomedicine may have the ability to create more sustainable and effective cures.

Functionalised selenium nanoparticles with amantadine allows for inhibition of the influenza virus through AKT signalling pathways. Selenium (Se), is a naturally occurring mineral found in soil, that has distinctive antimicrobial activities and the ability to regulate cellular redox homeostasis; these features protect cells from damage. This element combined with amantadine, an antiviral medication used to prevent and treat influenza, has shown excellent antiviral activity as evident in the academic article “Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signalling pathways” by. It was found that stable nanoparticles were created by modifying selenium nanoparticles (SeNP) with amantadine (AM). To measure cell viability Madin-Darby Canine Kidney cells (MDCK) with the H1H1 influenza virus (swine flu), was compared to MDCK cells with [email protected] particles. As evident in figure 1, the cell viability of the virus was at 32.34%, however, Se @AM increased the cells viability to 79.26%. This shows superior effectiveness to the treatment of cells. [email protected] allows for its nanoparticles to bind to neuraminidase (NA), the enzyme required for the influenza virus replication, therefore, stopping the binding of the virus to the MDCK cells. With the virus’s relative NA activity at 100%, however once paired with [email protected], the NA activity reduces to 36%. Furthering this, the NA activity was measured through a fluorescent product. This product was formed from the separation of the substrate 4-methylumbelliferyl-α-D-N-acetylneuraminic acid sodium salt hydrate solution during NA activity. Caspase-3 activity was used to measure cell apoptosis; this refers to particles that cause disease and the death of healthy cells. The caspase 3 activity for the virus was 519.7%. This is in comparison to [email protected] which caused a significant decrease in activity to 290.2%. Consequently, the reduction of caspase- 3 activity decreased the levels of reactive oxygen species (ROS), thus allowing for the development of AKT pathways which assist cells in the survival against the influenza pathogen.

Nanoparticulate vacuolar ATPase act as inhibitors and show effective treatment against the influenza virus infection. Vacuolar ATPases (V-ATPase) are proton pumps that function to acidify intracellular organelles within eukaryotic cells. The structure of these inhibitors allows for board-spectrum antiviral activity against influenza with low susceptibility to the virus rejecting drugs. Examples of ATPase’s include the hydrophobic compounds, dyphylline and bafilomycin, which have high toxicity and poor water solubility during clinical application. To overcome these factors, a poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA), nanoparticle system can be applied. PEG-PLGA nanocarriers improve the delivery of both dyphylline and bafilomycin through encapsulating water insoluble molecules. This allows for the improvement of water solubility which then causes the reduction of cytotoxicity, steadying the drugs pharmacokinetics. The technique of labeling has been applied in order to track the isotopes of both bafilomycin and diphyllin nanoparticles. To further show the effective drug delivery of nanoparticles, it can be seen that the groups treated with a higher dosage of 5 and 10 µM, show that diphyllin nanoparticles caused a substantial decrease in the H1H1 virus in comparison to the regular diphyllin. Similarly, as evident in figure 5, as the dosage for bafilomycin nanoparticles increases, its antiviral activity against the H1H1 virus also increases. As evident the highest dosage of 6.25nM significantly reduces the virus in comparison to the lower doses of 3.125nM and 1.56nM. It can be deduced that formulated diphyllin-loaded and bafilomycin-loaded nanoparticles enhance safety and reduce viral activities more efficiently than normal drugs. Therefore, nanoparticulate vacuolar ATPase inhibitors reduce the severity of the influenza virus whilst improving the survival outcome of cells. Gold nanoparticles induce protective immunity against the influenza A/H5N1 virus, suggesting effectiveness for a diagnosis kit for prevention of the pathogen. The H5N1 virus, also known as bird flu, is a sub virus of Influenza A, thus, it contributes to the most widespread pandemic of the pathogen. In order to combat this, the study of gold nanoparticles and their effect has been investigated.

Gold nanoparticles (AuNPs) have exceptional surface chemistry, optical and electronic properties, allowing for the successful application in biomedical science. Within the visible wavelength range, colloidal AuNPs can execute surface plasmon resonance (SPR). This refers to the oscillation of conduction electrons provoked by the electromagnetic of incident light. In addition to this, gold nanoparticles have the ability to fluently join to various biological molecules such as antibodies. Specifically, antibodies such as single chain fragment variables (scFv) can allow for the labeling of colloidal AuNP. This particular method of labeling is surmised by the academic journal, “Production of antibody labeled gold nanoparticles for influenza virus H5N1 diagnosis kit development”. Following this, the antibodies of scFv7 and scFv24 are specific to the glycoprotein found on the surface of the H5N1 virus; this is called the hemagglutinin (HA) surface antigen. Once the scFv7 labels the AuNPs a complex between nanoprobes and the antigen is created. As seen in Figure 6, the complex then travels to the scFv24 spotted membrane, allowing for the capturing of other HA surface antigens; this forms a red circular shape. Throughout the duration of 5-10 minutes, AuNPs move together on the surface of the membrane causing the dot to change from a light to vibrant red. This is due to the accumulation of AuNPs and their SPR characteristics, which cause combined vibrations of surface electrons induced by perceptible light of appropriate wavelength. Thus, gold nanoparticles show effective use in a dot plot activity which can be used as applicable materials for the development of an influenza A/H5N1 virus diagnostics kit.

However, whilst all these types of nanoparticles show effective treatment for the influenza virus, several limitations are still present. During the process of creating nanoparticles, the size range decreases and the number of surface atoms increase causing a significant increase in surface area. This increase can result in an enlarged chemical reactivity which raises uncertainty in regards to the effect of different conditions on particle reactivity and if they will be able to transport through cellular membrane. In addition to this, the augmentation of chemical reactivity within nanoparticles can cause a high production of reactive oxygen species (ROS). This can lead to inflammation, oxidative stress and cause damage to DNA, membranes and protein, thus generating toxicity concerns. In addition to this, the cost of nanomedicine is immense as surmised by the ETC group, Nanotech Rx, “the global health crisis doesn’t stem from a lack of science innovation or medical technologies; the root problem is poverty and inequality. New medical technologies are irrelevant for poor people if they aren’t accessible or affordable”. Furthering these limitations, proposed nanomedicine treatments can be used for wicked purposes if put in the wrong hands. For example, nanotechnology such as mechanisms that monitor the amount of insulin in diabetic individuals could be misused by governments. This raises ethical and privacy concerns as scientists may be reluctant on where to draw the line for the use of nanomedicine. Consequently, there is an array of limitations presented within the use of nanomedicine in the treatment of diseases, such as the influenza virus.

Influenza is one of the most infectious diseases on the planet, with widespread pandemics occurring every season and whilst there are treatments and prevention, these applications aren’t allowing for the greatest combat of the virus. However, with the induction of nanotechnology, nanoparticles have the potential to effectively treat and prevent the influenza pathogen due to their antibacterial and binding abilities. Several nanoparticles such as functionalised selenium nanoparticles with amantadine, nanoparticulate vacuolar ATPase act as inhibitors, and gold nanoparticles all show successful and effective mechanisms that combat this infectious disease. However, after the exploration of these types, it can be deduced based on evidence, that the functionalised selenium amantadine nanoparticles provide the most effectual applicability towards influenza. This is due to their ability to significantly increase cell viability whilst reducing the enzyme required for replication for the influenza virus, neuraminidase.

Therefore, nanomedicine, in specific nanoparticles exhibits several chemical mechanisms that allow for extremely effective treatments and prevention against the infectious influenza virus. However, to further extend this investigation of nanoparticles and their effect on influenza, more research can be conducted in order to gain a more detailed insight to how specific nanoparticles treat the disease.

14 May 2021

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