Nanomedicine and COVID-19

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Nanomedicine refers to the application of nanoparticles for the diagnosis, treatment and prophylaxis of diseases. Nanomedicine has been widely used to develop therapeutic interventions against various viral infections, including hepatitis B virus, human immunodeficiency virus, respiratory syncytial virus, influenza virus, and coronaviruses.

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Nanomedicines in coronavirus disease 2019

Nanoparticles used in nanomedicine exhibit unique physicochemical properties. The small size of nanoparticles allows them to easily cross intracellular barriers/membranes and interact with a variety of biological components of similar size. Additionally, the surface polarity of nanoparticles can be modified by various functional groups to increase their binding efficiency and stability and reduce aggregation and precipitation.

Given these specific properties, nanoparticles are increasingly being used to develop biomedical strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the coronavirus disease 2019 pandemic. (COVID-19).

Nanoparticles with antiviral properties, such as iron oxide, copper oxide, and silver nanoparticles, can be used to trap and inactivate SARS-CoV-2. These particles destroy viruses by disrupting the cell membrane, damaging proteins and DNA, forming free radicals, inhibiting biofilm formation, or exerting heavy metal toxicity. Recently, iron oxide nanoparticles have been shown to interact with the SARS-CoV-2 spike protein and alter its structural conformation.

These nanoparticles can be used in surface disinfectants and air filter systems to destroy SARS-CoV-2. Additionally, personal protective equipment (PPE) can be incorporated with antiviral nanoparticles to provide better protection for healthcare workers. For example, zine oxide nanoflower can be used in cotton fabrics to trap and destroy the virus.

Nanoparticles for the diagnosis of COVID-19

Rapid and accurate detection of COVID-19, contact tracing and isolation of infected people are the key measures to fight the pandemic. Nanoparticles can be modified to develop biosensors to detect a wide variety of diagnostic biomarkers, including DNA, RNA, proteins, enzymes, and antibodies. These nanoparticle-based biosensors provide a valuable platform for the rapid diagnosis of COVID-19.

Dual-function plasmonic biosensors are able to detect certain SARS-CoV-2 sequences with high sensitivity. These biosensors work by targeting the energetics of DNA-RNA hybridization. Graphene oxide nanoparticles coated with a target DNA sequence attached to a fluorophore have been developed to detect viral helicase. Additionally, graphene-conjugated anti-spike antibodies have been developed to detect SARS-CoV-2 in biological samples. This method requires no sample labeling or pretreatment and can detect SARS-CoV-2 at very low concentrations.

Nanoparticles for the treatment of COVID-19

Many strategies have been cultivated to use nanoparticles for COVID-19 treatment and drug delivery. In addition to directly targeting SARS-CoV-2, nanoparticles can be used as immunomodulatory agents to prime the immune system and prevent hyperinflammation in COVID-19 patients.

Graphene oxide nanoparticles have been found to enhance adaptive immune response and viral clearance by increasing levels of macrophages and T cells. Nano-diamonds play a vital role in reducing hyperinflammation by inducing anti-inflammatory macrophages. Similarly, carbon and graphene sheets can be modified to remove pro-inflammatory mediators (cytokines and interleukins) from the blood.

Lipid nanoparticles have been used for targeted delivery of SARS-CoV-2-specific small interfering RNAs (siRNAs) into the lungs and suppression of viral replication. Polylactic-co-glycolic acid polymer-based nanosponge has been developed to prevent SARS-CoV-2 from infecting cells. The nanosponge was coated with a human lung epithelial cell and macrophage membrane to mimic the cell physiology required for SARS-CoV-2 host cell entry. This synthetic cellular nanosponge acts as a target for SARS-CoV-2 and neutralizes the virus.

Liposomes, which are lipid bilayer vesicles, serve as a powerful platform for drug delivery. Synthetic peptide-based liposomes have been developed to eliminate SARS-CoV-2 by inducing cytotoxic T cells. An inhalable formulation based on hydroxychloroquine liposomes has been developed and tested in rats. The formulation has been shown to increase drug concentration in the lungs by 30 times.

A cyclodextrin-based formulation of remdesivir recently received US Food and Drug Administration (FDA) approval for the treatment of COVID-19. Cyclodextrin nanoparticles are cyclic polysaccharide-based particles widely used in pharmaceutical companies as solubilizers to dissolve hydrophobic and hydrophilic drugs.

Covid vaccine

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Nanoparticles for COVID-19 vaccination

Two mRNA-based COVID-19 vaccines formulated with lipid nanoparticles containing the SARS-CoV-2 spike protein as a target immunogen have received FDA approval. These two vaccines (mRNA-1273 vaccine from Moderna and BNT162b2 vaccine from Pfizer/BioNTech) have been shown to be more than 90% effective in preventing SARS-CoV-2 infection and symptomatic COVID-19, both in clinical trials than in real settings.

Two nanoparticle-based COVID-19 vaccine candidates are currently in development. For example, the NVX-CoV2373 vaccine (Novavax) containing a trimeric spike protein as an antigen has been shown to induce spike-specific neutralizing antibodies and a T-cell response in human clinical trials. Another nanoparticle-based vaccine candidate containing a spike receptor-binding domain (RBD) as its antigen has shown similar immune responses in preclinical and clinical trials.

SpyTag/SpyCatcher technology is a widely used covalent fusion system for the irreversible conjugation of recombinant proteins. In a Chinese nanovaccine candidate, this technology was used to conjugate the RBD spike with ferritic nanoparticles. This candidate vaccine has been shown to induce long-lasting antibody and memory immune responses in mice for at least 7 months.

Taken together, nanomedicine is considered a promising approach for the diagnosis, treatment and prevention of COVID-19.

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