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The Applications Of Nanomaterials Against Viral Disease - News-Medical.net
Nano-based therapeutics and diagnostic systems are being increasingly applied to various fields of medicine, acting as sensors, delivery vehicles, immunostimulants, radiation sensitizers, and viral inhibitors. In a paper recently published in the journal Pharmaceutics, the application of nanomaterials in the diagnosis, prevention, and treatment of viral diseases is reviewed in detail, highlighting areas of significant progress or stagnation from the past few decades.
Study: Application of Nanomaterials as an Advanced Strategy for the Diagnosis, Prevention, and Treatment of Viral Diseases. Image Credit: Love Employee/ Shutterstock
Nanomaterials in diagnosisNanomaterials encompass any engineered structure with a monomeric unit in the size range of 1-100 nm. They, therefore, include macroscopic materials with nano-scale surface features and microscopic particles in the nano-size range.
Carbon nanotubes are hollow cylindrical structures with intriguing electric properties that facilitate use in biosensors by incorporation of a specific protein or nucleic acid probes. For example, conjugation with complementary DNA or RNA to the virus being detected creates a high-speed virus sensor with a very low detection limit, where fluctuations in current through the sensor can be used to infer viral load. Flat graphene sheets of carbon can similarly be bound with antibodies or DNA to create sensors that can interact with larger biomolecules than carbon nanotubes owing to a lower degree of curvature exhibited.
Gold nanoparticles exhibit unique light interactions that result in intense adsorption across a narrow range of wavelengths, a phenomenon known as surface plasmon resonance. The wavelength of light most strongly absorbed by the particles is dependent on particle shape and size and can be tuned from the visible to the near infra-red.
Near infra-red light is maximally penetrating through biological tissue, and therefore sensors that rely on optical signaling in this range are ideal as a diagnostic platform. As with carbon nanotubes, relevant complementary molecules can be attached to the particles that will only bind with the virus or antibody under investigation.
Similarly, the specific wavelength of light in resonance with the particles can also be influenced by proximity with other particles. Thus, by inducing inter-particle bonding, the presence of a compound of interest can be determined colorimetrically by the eye. Many lateral flow severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection assays are based on the use of gold nanoparticles, where particles bearing a DNA reporter probe are combined with viral RNA in the sample to generate a visible red line.
Nanomaterials in disease preventionNanomaterials have been intrinsic to the development of coronavirus disease 2019 (COVID-19) vaccines, the mRNA-based vaccines utilizing liposomes or lipid nanoparticles as a delivery vehicle. Outside of the cytoplasm, mRNA degrades quickly, and thus liposomes ensure that the payload enters the cell and is available for transcription. An mRNA-based vaccine utilizing liposomes was first developed in 1993 against the influenza virus. Since then, liposomes have been exploited to deliver sensitive biomolecules into the cell in several capacities, such as during CRISPR-Cas9 gene editing.
Nanomaterials are also frequently used as adjuvants in vaccine formulations to stimulate an intense immune response, first employed in a seasonal flu vaccine in 1997 with the incorporation of squalene droplets coated in biocompatible surfactants. Since then, the conjugation of viral antigens onto the surface of nanoparticles has shown great success in stimulating an immune response in several vaccine formulations.
Nanomaterials in disease treatmentDrug delivery is the major purpose of nanomaterials in disease treatment, generally offering improved pharmacokinetics, drug retention time, and the "drug-likeness" of the compound being delivered.
The physical and chemical properties of the nanoparticle strongly influence the biodistribution of the nanomedicine in the body and the ability and propensity of the particle to enter target cells.
Tuning the surface charge, size, and outwardly presenting the chemical character of the particle can encourage uptake specifically to areas of inflammation, and further specificity can be imparted by incorporating target ligands onto the particle's surface. For example, attaching an antibody against the spike protein of SARS-CoV-2 can encourage the uptake of the particle into infected cells that are presenting the relevant antigen.
The large surface-to-volume ratio of nanomaterials provides an ample platform on which both targeting ligands and drug payloads may be loaded, allowing for the simultaneous delivery of large quantities of multiple compounds with synergistic effects.
Besides use as a delivery vehicle, nanoparticles themselves may be utilized as virus therapeutics, acting to block the viral replication cycle or cell entry. Silica nanoparticles designed to bind with the influenza virus have shown efficacy in blocking viral entry into cells in this way. Particles constructed from copper, silver, and gold are also capable of generating reactive oxygen species. Besides being directly damaging to viral genetic material can induce apoptosis in infected cells, thereby preventing viral propagation. Such materials can also be coated on high-traffic surfaces such as handrails to destroy any virus or bacteria by exposure to reactive oxygen species.
Immunoregulatory Nanomedicines For The Prevention And Treatment Of ...
In a recent study published in the journal Nature Reviews Bioengineering, researchers explore various aspects of immunoregulatory nanomedicines against respiratory illness.
Study: Immunoregulatory nanomedicine for respiratory infections. Image Credit: mi_viri / Shutterstock.Com
Respiratory diseases and immunotherapeuticsRespiratory infections are one of the leading causes of global mortality and morbidity. Moreover, these illnesses significantly affect the global economy, social development, and healthcare systems.
Respiratory diseases are caused by various pathogenic viruses, bacteria, and fungi, the most notable of which include Middle East respiratory syndrome (MERS) coronavirus, H1N1 influenza, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, pulmonary aspergillosis, tuberculosis, and bacterial pneumonia.
Vaccination and immunotherapy are effective immune-based strategies to prevent and treat infectious respiratory diseases. These immunoregulatory treatments manipulate the therapeutic functions of the immune system, as vaccination stimulates adaptive immunity to protect against pathogenic infestation.
There are different types of vaccines based on differential developing strategies, such as whole-inactivated pathogens, live attenuated pathogens, recombinant bacterial vectors, recombinant viral vectors, synthetic peptides, DNA, and messenger ribonucleic acid (mRNA).
Typically, subunit vaccines have limited immunogenicity, as they contain fewer antigens, thereby preventing them from producing significant immune protection against the pathogen. Recently, SPIKEVAX and COMIRNATY, both of which are two nanovaccines, received approval from the United States Food and Drug Administration (FDA) for the prevention of the coronavirus disease 2019 (COVID-19).
Antibody treatments are effective in treating early-stage viral infections. In addition, immune potentiator molecules, such as Toll-like receptors and inflammation modulator molecules, including interleukin-1 (IL-1) or IL-6 receptor antagonists, are used to treat respiratory illness. These strategies are associated with translational challenges that lead to reduced antibody titers in plasma over time and insignificant therapeutic efficacy due to viral mutations.
Nanomedicines based on different nanocarriersNanomedicines are designed to enhance the therapeutic outcomes of drugs, primarily by improving drug loading capacity and release, which enhances their pharmacokinetic properties. Peptides, micelles, cell membranes, extracellular vesicles, liposomes, and polymers can be designed as nanocarriers. A nanocarrier can regulate the immunological environment for effective respiratory disease treatment.
Ionizable nanoparticles (iLNPs) are commonly used to deliver mRNA, as they protect this genetic material against non-specific protein binding. This nanocarrier is electrically almost neutral, and negatively charged mRNA is loaded under acidic pH conditions. The nebulization technique is used to efficiently deliver mRNAs from iLNP to the lungs.
Cationic polymers are used to deliver nucleic acid for therapeutic purposes; however, this technique is rarely used in clinical settings due to the risk of toxicity observed in vivo. A recent study revealed that a nanocarrier containing polyethyleneimine (PEI) was used to deliver a plasmid DNA vaccine through the intranasal route for COVID-19 prevention and treatment.
Protamine is a positively charged small protein that is rich in arginine. This protein is used to deliver mRNA for the prophylactic vaccination against respiratory illness caused by influenza A H1N1, H3N2, and H5N1 viruses. Polycation-functionalized zirconium (Zr)-based metal-organic frameworks and DNA-decorated gold nanoparticles have also been explored for mRNA delivery.
Nanomedicines-regulated immune systemA local inflammatory response arises during lung infection if alveolar macrophages fail to control pathogenic growth. Initially, alveolar epithelial cells are activated by recognizing pathogen-associated molecular patterns (PAMPs).
Macrophages, activated alveolar epithelial cells, and other immune cells secrete pro-inflammatory cytokines to bring more immune cells to the infected lung tissues. In some cases, massive production of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) cause aggressive inflammatory response syndrome, which can lead to severe respiratory infections and even death.
Immune-regulating nanomedicines can improve therapeutic efficiency by blocking pro-inflammatory signaling pathways and inhibiting the entry of viruses. Nanomedicines can modulate hyperactivated immune cells and scavenge unsolicited immune molecules. Nanotherapeutics can also inhibit neutrophil function by downregulating superoxide anions, thereby suppressing neutrophil elastase and blocking β2 integrin signaling, which helps reduce persistent lung inflammation.
The size of nanoparticles affects neutrophil deactivation. For example, small nanoparticles loaded with oleic acid exhibited greater neutrophil deactivation by suppressing the production of superoxide anions and neutrophil elastase. Comparatively, larger nanoparticles accumulate in the lung tissues without alleviating lung infection.
ConclusionsSeveral studies have shown that the application of immune-regulation strategies could significantly improve the prevention and treatment of infectious respiratory diseases. An effective application of nanoparticles, particularly for drug delivery, can dramatically improve disease outcomes.
Nanovaccines can activate both B-cell and T-cell responses and can be easily modified in accordance with new viral mutations. Inhalable nanovaccines can also be developed to deliver antigens directly into the lungs; however, these vaccines must be equipped to overcome the barriers of the mucosal system.
More research is needed to determine the safety profile of these vaccines and their possible distribution to the central nervous system. In the future, artificial intelligence can be used to select and design antigen molecules for the development of effective nanovaccines.
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