Application of Nanomaterials as an Advanced Strategy for the Diagnosis, Prevention, and Treatment of Viral Diseases

Abstract

The coronavirus disease (COVID-19) pandemic poses serious global health concerns with the continued emergence of new variants. The periodic outbreak of novel emerging and re-emerging infectious pathogens has elevated concerns and challenges for the future. To develop mitigation strategies against infectious diseases, nano-based approaches are being increasingly applied in diagnostic systems, prophylactic vaccines, and therapeutics. This review presents the properties of various nanoplatforms and discusses their role in the development of sensors, vectors, delivery agents, intrinsic immunostimulants, and viral inhibitors. Advanced nanomedical applications for infectious diseases have been highlighted. Moreover, physicochemical properties that confer physiological advantages and contribute to the control and inhibition of infectious diseases have been discussed. Safety concerns limit the commercial production and clinical use of these technologies in humans; however, overcoming these limitations may enable the use of nanomaterials to resolve current infection control issues via application of nanomaterials as a platform for the diagnosis, prevention, and treatment of viral diseases.

Keywords: diagnosis; nanomaterials; therapeutics; vaccines; viral diseases.

Figure 1

Application of nanomaterials for diagnosis with advanced sensitivity and selectivity. (a) Schematic of using carbon nanotubes for H5N2 isolation and concentration, directly from in situ samples. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of H5N2 separated by carbon nanotubes are shown. Reproduced with permission from [30]. Copyright (2016) American Association for Advancement of Science. (b) Schematic representation of graphene as a sensing material for detecting SARS-CoV-2. The SARS-CoV-2 spike antibody binds to graphene and the reaction with the target is converted into an electrochemical signal. Reproduced with permission from [31]. Copyright (2020) American Chemical Society. (c) AuNP-based colorimetric diagnosis of coronavirus disease (COVID-19). The surface-modified AuNPs with antibodies bind to the virus, which shifts the absorption wavelength of AuNPs. The shift in absorption wavelength changes the color of AuNPs from red to purple. Reproduced with permission from [32]. Copyright (2020) American Chemical Society. (d) Synthesis schematic of CdSe/CdS/ZnS quantum dots (QDs) and mechanism of application in rapid diagnostic strips. TEM images and fluorescence spectrum of synthesized QDs. Influenza A virus was detected using the fluorescence emission spectrum of the QDs on the rapid diagnostic strip. Reproduced with permission from [33]. Copyright (2020) Elsevier.

Figure 2

Overview of nanoplatform-based vaccines approved by the World Health Organization (WHO) for the prevention of emerging infectious diseases. Viral vectors and lipid NPs (LNPs) elicit potent immune responses by stably delivering DNA and mRNA encoding antigens, respectively, to antigen-presenting cells.

Figure 3

Antigen and immunostimulant delivery using nanoparticles. (a) Schematic showing the preparation of a viromimetic nanoparticle vaccine using hollow PLGA nanoparticles with encapsulated adjuvant and surface maleimide linkers for conjugating viral antigens. Protection efficiency of vaccinated hDPP4 transgenic mice against lethal infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Statistical analyses were performed by unpaired t-tests (* p < 0.05, ** p < 0.01, *** p < 0.001). Reproduced with permission from [120]. Copyright (2019) Wiley. (b) Schematic of solid-core NP and watery-core polymersome (PS). Proportions of IFNγ-producing CD4+ and CD8+ T cells in the spleen, lymph nodes, and lungs after immunization with NP and PS. The non-parametric Manne-Whitney U-test was used to compare experimental groups (* p < 0.05; ** p < 0.01; *** p < 0.001; ns, not significant). Reproduced with permission from [121]. Copyright (2013) Elsevier. (c) Schematic showing inhalable bionic-virus nanovaccine activating cellular immunity and humoral immunity of respiratory mucosa. TEM images of bionic-virus particles. Scale bars, 200nm. Antigen-specific immune responses (IgG, IgA titer, and inhibition titer) upon immunization with inhalable bionic-virus nanovaccine. (I: PBS, II: Intramuscular Injection, III: Intraperitoneal Injection, IV: Nasal Delivery) Reproduced with permission from [122]. Copyright (2021) Elsevier.

Figure 4

Nanoparticulate aluminum-based adjuvants. (a) Schematic representation of aluminum hydroxide-PpAS nanoparticles (APNs) adsorbing OVA and CpG. APNs promote antigen cross-presentation via a cytosolic pathway in dendritic cells. Enhanced antigen-specific humoral and cellular immune responses after immunization with APNs. Statistical analysis was performed using one-way ANOVA, followed by the Bonferroni post-test. * p < 0.05; ** p < 0.01; ^# p < 0.05; ^### p < 0.001; ns, not significant; nd, not detectable. Reproduced with permission from [132]. Copyright (2018) American Association for Advancement of Science. (b) Schematic of the surface charge functionalization of aluminum oxyhydroxide [AlO(OH)] with APTES and HSPSA. Representative TEM images of ALNR, ALNR-NH2, ALNR-SO3H and ALNR-C, where the scale bars was 200 nm. NLRP3 inflammasome activation after treatment with ALNR has also been shown. Statistical analysis was performed using Tukey’s test. The values that do not share the same letter indicate statistical differences at p < 0.01. Reproduced with permission from [131]. Copyright (2017) American Chemical Society.

Figure 5

(a) Characterization of phenyl boronic acid (PBA)-conjugated polymersome (PBASome)-controlled inter-ligand distance between PBA conjugates. (b) Confocal laser scanning microscopy (CLSM) images of PBASomes in the presence of various weight fractions, as observed when stained for lectin. Green, fluorescein isothiocyanate; blue, DAPI; red, WGA. Reproduced with permission from [146]. Copyright (2018) Royal Society of Chemistry. (c) Enhanced expression of RIG-I and IFN-β in A459 cells treated with GNR-5′PPP-ssRNA indicates inhibition of infection by H1N1 influenza virus and Solon Islands seasonal flu strain. (d) Inhibition of viral replication of the 2009 pandemic H1N1 influenza virus and Solomon Islands seasonal flu strain in the presence of GNR-5′PPP-ssRNA, evaluated in A459 cell lines. Reproduced with permission from [169]. Copyright (2010) National Academy of Sciences. (e) Schematic of the mechanism of T-Fc-IVM-NP in HEK293T via decreased ACE2 expression and viral uptake. (f) Inhibition of ACE2 expression and pseudovirus uptake in HEK293T cells were evaluated using therapeutic (left) and preventative (right) treatment methods. Reproduced with permission from [170]. Copyright (2020) American Chemical Society.

Figure 6

(a) Scheme for polymeric nanoparticle (PGs) conjugated with peptide (PeB) in various molecular weights is represented. (b) Inhibition of influenza A virus infection by PG-PeBs, prepared using different molecular weights of PeBs, was evaluated in vitro (top) and in vivo (bottom) (*** p < 0.001). Reproduced with permission from [175]. Copyright (2017) Wiley. (c) Schematics showing the synthetic process of curcumin-derived copper QDs (Cur-CQDs) (top) and their mechanism of antiviral activity (bottom). (d) Therapeutic effect of Cur-CQDs against enterovirus 71 (EV71) infection was evaluated in an in vivo study. Survival rates, clinical scores, and body weights of (i) mice without infection and mice injected with (ii) PBS, (iii) curcumin, or (iv) Cur-CQDs, followed by challenge with EV71. Reproduced with permission from [179]. Copyright (2019) Wiley. (e) Antiviral activity of silver nanoparticles decorated with antiviral agents (Ag@OTV) was evaluated by determining the viability of H1N1-infected cells (top) and analyzing the ROS production detected based on DCF fluorescence intensity (bottom) in H1N1-infected cells. One-way analysis of variance (ANOVA) was used for statistical analysis. Data represent mean ± standard deviation (* p < 0.05 or ** p < 0.01) (f) TEM image cell sections treated with control media (left), virus (middle), and virus + Ag@OTV (right), where the scale bars were 1 μm (left), 200 nm (middle), and 200 nm respectively. (g) ROS-mediated apoptotic signaling pathway, as well as p53 and AKT signaling pathways, are regulated by Ag@OTV. Reproduced with permission from [181]. Copyright (2016) American Chemical Society.