Home Efficacious nanomedicine track toward combating COVID-19
Article Open Access

Efficacious nanomedicine track toward combating COVID-19

  • Sameh A. Mohammed EMAIL logo and Esraa Ibrahim A. Shaaban
Published/Copyright: January 28, 2022
Download Article (PDF)
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Nanotechnology Reviews
From the journal Nanotechnology Reviews Volume 11 Issue 1

Abstract

COVID-19 outbreak has become one of the catastrophic health emergencies that could threaten public health worldwide through several hospitalizations and thousands of deaths, leading to boosting global concern intensive precautionary measurements. The clinical and research trials are ongoing for developing several diagnostic tools, antiviral therapeutics, and vaccines versus COVID-19 infectiousness. This review argues the recent nanomedical progress and efficient nanomedicine applications and highlights relevant challenges and considerations of nano-based materials for combating COVID-19 infectiousness and severity. Eventually, we also provide futuristic avenues and perspectives paving the way to explore outstanding solutions for SARS-CoV-2 control and eradication.

Keywords: COVID-19; nanomedical diagnostics; nano-based therapeutics and vaccines

1 Introduction

The first identification of SARS-CoV-2 took place in December 2019, which belonged to Coronaviridae family and encompassed a massive variety of regularly widespread viruses in animals and humans. The major manifestations in humans are a mild respiratory or digestive disturbance [1]. Otherwise, minor coronaviruses have dense and severe respiratory disorders leading to lethal outbreaks [2,3]. Comparable to SARS-CoV-1 and MERS-CoV, SARS-CoV-2 possesses characteristic features of rapid transmission among human beings to be categorized as the largest global public health menacing to humanity in this century [4]. As the majority of patients with COVID-19 are asymptomatic, the transmission of COVID-19 among persons is glaringly high [5]. Basically, the critical step of COVID-19 pathogenesis is SARS-CoV-2 intracellular entry through binding of S protein to angiotensin-converting enzyme (ACE) surface receptors that are specific receptors facilitating SARS-CoV-2 invasion of the host and then endosomal encapsulation and eventually the lysosomal and viral membrane fusion [6,7]. The spike proteins could stick tightly to glycans of mucins in the mucus that line the airway epithelium; hereby SARS-CoV-2 possesses the capability to remain in the airways (Figure 1). Based on the significance of S protein, effective targeting by inhibition of its activity exhibits one of the targeting options of COVID-19 cures displaying SARS-CoV-2 viral blockage [8,9]. The M protein is classified as a transmembrane glycoprotein type III, the most common protein predominating on the surface of SARS-CoV-2 [10]. M protein could organize the viral assembly during its binding to N protein for the nucleocapsid. The virion stabilization and M protein also regulate the interaction with other structural proteins [11,12,13]. The N protein is a remarkable protein in the SARS-CoV-2 genome that plays a fundamental role in the formation of nucleocapsids via supporting the viral genome conjugation with arginine and lysine amino acids [14,15]. Moreover, several studies have reported that the high expression of N protein is correlated with significant boosting in the viral-like particles (VLPs) production and assembly leading to maturation of formed virion [16,17]. Eventually, the smallest protein is E protein, a 10–74 kDa molecular weight. Higher E protein expression within host cells has been noticed during the viral life cycle, whereas a little fraction is integrated into the package of the mature virion [18,19,20].

Figure 1 SARS-CoV-2 structure and mechanism for remaining in the airways via spike protein.
Figure 1

SARS-CoV-2 structure and mechanism for remaining in the airways via spike protein.

In March 2020, The World Health Organization endorsed that the COVID-19 outbreak had become a pandemic due to a massive number of infectious cases with an accelerated mortality rate. Fever, cough, and tiredness are the main symptoms and shortness of breath, headache, and loss of smelling or/and tasting sensation are the less common symptoms of COVID-19. Moreover, elevated blood pressure and coronary heart disease may present in case of severe cases [21,22].

2 Nanomedicine track against COVID-19 infectiousness

Nanotechnology applications have become a pillar part of industrial and translational researches these few years. To be more specific, the nanomedicine term is carefully designed for nanomedical purposes, such as diagnosis, prevention, and therapy of diseases [23]. As demonstrated in Figures 2 and 9, nanomaterials or nanoparticles provide a wide variety of approaches in the manufacture of diagnostic kits and in the ongoing development of antiviral therapeutics and vaccines. Ameliorative modification in physicochemical characterizations, lower adverse effects, higher drug delivery efficiency, and higher bioavailability have been provided as outstanding advantages for recruiting nanomaterials against COVID-19 [24]. These unique features of nanomaterials could enable them to easily overlap with viral entry or host cell receptor attachment [25]. Below, we will manifest an overview of nanomaterials along with their clinical applications in COVID-19 diagnosis, vaccination, and treatment.

Figure 2 Nano-sized materials utilized in diagnosing, fighting, and preventing COVID-19.
Figure 2

Nano-sized materials utilized in diagnosing, fighting, and preventing COVID-19.

2.1 Nanoparticles for diagnosis of COVID-19

Currently, the RT-PCR test and serologic diagnostic test are widely harnessed in the detection and screening of the virus in specimens. The detailed steps in the RT-PCR test procedure are illustrated in Figure 3.

Figure 3 The diagnostic steps in PCR test for the COVID-19 detection. Procedures include the collection of samples and viral RNA extraction. By reverse transcription process, cDNA will be generated to obtain the amplification plot. A fluorescent signal is readily used to detect the viral cDNA.
Figure 3

The diagnostic steps in PCR test for the COVID-19 detection. Procedures include the collection of samples and viral RNA extraction. By reverse transcription process, cDNA will be generated to obtain the amplification plot. A fluorescent signal is readily used to detect the viral cDNA.

Cellex Inc had manufactured a new rapid test as a serological immunodetection, qSARS-CoV-2 IgG/IgM rapid test (Figure 4), which has been recently approved by the FDA [26].

Figure 4 Serological immunoassay of qSARS-CoV-2 IgG/IgM rapid test for the detection of COVID-19 antibodies.
Figure 4

Serological immunoassay of qSARS-CoV-2 IgG/IgM rapid test for the detection of COVID-19 antibodies.

The ongoing progress on conventional tools for the diagnosis of COVID-19 by researchers to tackle their various limitations, for instance, false-negative results, longer evaluation time, and lack of sensitivity and specificity [27,28]. Harnessing quantum dot nanocrystal, magnetic and metal nanoparticles, ranged from 2 to 60 nm for conducting rapid COVID-19 detection.

Infectious pathogens possessing advanced nanosensing characteristics were primarily detected via versatile quantum dot nanocrystals. The most common commercial nanocrystals, the MHC-Ig avidin-biotin tagged coupling and the complex anti-CD28 antibodies on the top of a polymer-coated quantum point have readily constituted a quantum dot artificial antigen-presenting cell (aAPC). The incidence of CD28 T cells proliferation, once the exposure of antigen-presenting cells induced by quantum dot aAPCs, is higher 15 times than controls [29]. Fluorescent quantum dots can also be used to detect coronaviruses. One of the major steps of COVID infection is S protein receptor attachment to the host cell ACE2 receptors on the plasma membrane. Now, the recombinant spike receptor is conjugated with quantum points to synthesize multilateral imaging probe. The specific diagnostic reaction was regarded as neutralization of anticörper and human recombinant ACE2 blocked quenching. The additional function of this unique nanoparticle-based probe has obviously demonstrated in the validated identification of S protein and ACE2 receptor attachment inhibitors [30]. Quantum dot-tagged RNA aptamer particularly for the SARS-CoV N protein was tremendously susceptible for immobilized protein detection of virus [31]. For swift screening and detection of IgG antibodies generating against COVID-19, immunoassay strips are widely utilized [32]; for instance, a concise IgM antibodies detection relied on versatile colloidal gold nanoparticle (Au-NP) multilateral flow assay [33] or double-functional photothermal biodetectors for coronaviruses [34].

Iron oxide nanoparticles (IO-NPs) are the popularly used magnetic-based nanoparticles, characterized with marvelous magnetic efficiency [35]. There are a variety of important applications recruiting these nanoparticles, such as newly developed Cdn detectors in coronaviruses similarly to harnessing silica nanoparticles in PCR assays [36]. In this assay, magnetic-bonded dsDNA conjugates are regularly synthesized, and also nontargeted cDNA is easily identified through the reaction of oligonucleotide probes with silica-encapsulated superparamagnetic nanoparticles. The magnetoplasmonic nanoparticles were additionally utilized to ameliorate the diagnostic RT-PCR method of SARS-CoV-2 when entered in a combination with poly(aminoester) and carboxyl groups. This pattern uses probe-functionalized magnetoplasmonic nanoparticles to enhance the viral RNA targeting [37]. Furthermore, the interesting advantages of biomimetic-functionalized magnetoplasmonic nanoparticles, such as smaller size, tremendous magnetic features, and saving biodetection time, have basically acquired them valuable preference for their multiple applications, especially in the detection of various pathogens.

Nanopore target sequencing, as shown in Figure 5, which has been developed by Oxford Nanopore Technologies, Oxford Science Park, UK is recently utilized for COVID-19 detection. This novel technique is based on the amplification and sequencing of 11 virulent and specific SARS-CoV-2 genome fragments (ORF1ab) [38] along with encoding other structural parts, for example, ORF7a, ORF8, S, E, M, N, ORF3a, and ORF10.

Figure 5 Nanopore SARS-CoV-2 genome target sequencing consists of the preparation of clinical samples for RNA extraction and cDNA synthesis for PCR implementation, rapid barcoding, and genome sequencing.
Figure 5

Nanopore SARS-CoV-2 genome target sequencing consists of the preparation of clinical samples for RNA extraction and cDNA synthesis for PCR implementation, rapid barcoding, and genome sequencing.

Surface plasma resonance represents a characteristic property of metal nanoparticles, such as copper, gold, and silver, which could govern the size modification of these nanoparticles depending on their morphology [39]. Au-NPs are the most functionalized metal nanoparticles used for the detection of coronaviruses. The antisense oligonucleotides targeted the N gene is utilized in a combination with Au-NP to detect the viral N gene resulting in high aggregation of Au-NPs [40,41]. Furthermore, silver nanoparticles (Ag-NPs) were also mainly used for MERS-CoV detection by a color change in the colorimetric assay method for the rapid estimation of viral target cDNAs.

There is a modern study focusing on nano-based diagnosis of SARS-CoV-2 with poly carboxyl-functionalized magnetic nanoparticles. This trend has offered promising outcomes through 20 min working time and the highest detection sensitivity (even ten copies) for COVID-19 molecular diagnosis [42]. The diverse applications of nanomedicine are not limited only to PCR figuring but also in further techniques, such as reverse transcription loop-tagged isothermal amplification and enzyme-linked immunosorbent assay [43]. For example, Zhu and colleagues also reported the nanoparticle-related biosensor platform for COVID-19. This platform is a simple track showing a one-step reaction procedure for an hour of result delivery [44]. Eventually, Mertens exhibited a recent method based on silver Respi-Strip diagnostic assay [45]. Recently, protein corona sensor technique and magnetic levitation assay have been proposed as multidisciplinary nanotechnology-based diagnostic methods for the detection of high-risk individuals at the early phase of COVID-19 infection [30,46], thus, prioritizing the proper patients, and evaluating plasma protein and biomolecule patterns, as well as minimizing the economic and social pressure leading to lowering the mortality rate among high-risk patients due to serious COVID-19 complications, for example, sudden blood clots. Table 1 summarizes the main features of different types of nano-based materials used for COVID-19 diagnosis.

Table 1

Characterizations of different types of nanoparticles used for COVID-19 diagnosis

Types Examples Size (nm) Composition Surface charge Biodetector type Ref.
Inorganic nanoparticles Quantum dots 2–10 Composed of Hg, Pb, Zn, and Cd, e.g., CdSe, CdTe +/or − Electrochemical and optical [29,30]
Magnetic nanoparticles (IO-NPs, zinc oxide NPs) 2–20 Fe2O3, γ-Fe2O3, Fe3O4, and ZnO +/or − Electrochemical [35]
Metal nanoparticles (gold, silver, copper NPs) 1–60 Au, Ag, and Cu +/or − Electrochemical and optical [39,40,41,64]
Organic nanoparticles Graphene oxide (GO) NPs 40–200 GO — Electrochemical and optical [35]

2.2 Nanoparticles in COVID-19 therapy

Several studies have discussed the use of different nanomaterials as facilitators or carriers of treatment patterns for greater antiviral effectiveness in combating COVID-19 infectiousness. One of these examples, lipid-based carriers for salinomycin intrapulmonary delivery in COVID-19 infected patients. Many researchers have argued this drug in COVID-19 infection as a result of the supposed relationship of COVID-19 severity with dietary styles and commensal microbiome via designing efficacious foods and smart therapeutics for targeting problematic pathogens in the intestinal gut as a sort of supplementary agent for COVID-19 [47,48].

As revealed in Figure 6, salinomycin is a potential antiviral agent, works on the interference with S protein of SARS-CoV-2 for ACE2 receptors binding on the surface of host cells in a pH-dependent manner, thus preventing the viral fusion with the host cell membrane to release viral genetic material into the cytoplasm leading to hindering viral entry without induction of viral infection [49,50]. Due to its good physicochemical properties of salinomycin, it could be aerosolized efficiently by droplets to obtain good adherence of the lung’s mucosal surface and for prolongation of release time to be considered as a prospective therapeutic nanomedicine-based potential against SARS-CoV-2 infection [51]. The encapsulation of salinomycin by using lipid-based nanostructures as a nanocarrier pattern because of their extraordinary aerodynamic characterizations led to gradually boosting the absorption of salinomycin in the lung of infected patients [52].

Figure 6 Lipid-based nanoparticles for pulmonary salinomycin delivery in the treatment of COVID-19 infected patient.
Figure 6

Lipid-based nanoparticles for pulmonary salinomycin delivery in the treatment of COVID-19 infected patient.

A recent in vitro study by Zhang et al. harnessed the plasma membrane of human cells for synthesis of two forms of nanosponges, for example, alveolar epithelial cells and macrophages to induce SARS-CoV-2 neutralization [53]. Moreover, these nanosponges revealed higher binding and attaching to SARS-CoV-2 to optimize the neutralization than displayed in ACE2 receptors overexpressed on the outer surface of host cells, therefore, blocking the viral-cellular entry. Another report conducted by Ting et al. successfully cultured the Vero cells to experimentally investigate the porcine epidemic diarrhea virus (PEDV) as a similar pattern to those of SARS-CoV through curcumin (CCM) delivery by stable carbon dot encapsulation of CCM for delivery using these intelligent nanomaterials [54]. The resultant findings of this study suggested that these carbon dots inhibited both ROS accumulation induced by PEDV and viral RNA synthesis and budding, thus altering the uniform shape of SARS-CoV-2 surface proteins and eventually hampered its entry for host cell infection. This inhibition of ROS accumulation in host cells assisted in limited SARS-CoV-2 expansion and is expected to damage DNA, which could lead to downregulation of a set of cellular apoptotic pathways, inflammatory cytokine production, and interferon-stimulating genes [55,56]. A further similar study that discussed different nanomaterials, silver sulfide-loaded glutathione nanoclusters, have been examined for efficient delivery of glutathione as a powerful antioxidant to host cells exhibiting promising outcomes for the suppression of SARS-CoV-2 replication [57]. Opposing stable carbon dots, this research reported that this type of nanomaterials positively overexpressed inflammatory cytokines and interferon-stimulating genes, hence causing innate immunity activation against the virus. Considering together, these promotive findings indicate the significant role of various inorganic nanoformulations as fundamental contributors in the suppression of SARS-CoV-2 viral proliferation and replication for combating its infectiousness. Additionally, Chen and coauthors utilized GO sheets-coupled Ag-NPs to suppress feline coronaviruses, approximately 25% infection inhibition in cell culture [58]. GO bound to feline CoV lipophilic tails, whereas Ag-NPs attached to thiol group in E protein of the virus, thus resulting in subsequent aggregation and rupture. This platform seemed to be considered in clinical practice to generate frontier effects for presenting new therapeutic nano-based modality along with intrasuppressive features in relevance for combating SARS-CoV-2 infection [59,60]. Peptide-mediated lipid nanoparticles (LNPs) represented one of the most common nanostructures functionalized for antivirals or vaccines delivery against COVID-19; for example, Ansari and colleagues have published a study emphasizing the use of lipid-based nanoparticles for improving the effectiveness of repurposed therapeutics against the virus [61]. Due to its biocompatibility and cell penetrability plus its high stability and capacity to customize it for cinematically accurate and long-term release of drugs, peptide-mediated LNPs had been taken into consideration to create state-of-the-art bioengineered systems possessing attractive characterizations for life-threatening health hazards specifically in the emergent of COVID-19. Interestingly, there is a current direction of mesenchymal stem cell transplantation for the treatment of infected patients with COVID-19 [62]. A recent study reported the importance of exosomes synthesized from mesenchymal stem cells in comparison with other fabricated nano-derived vesicles [63]. Safety, high biocompatibility, and lack of immunogenic levels are a variety of characterized merits for cellular targeting and fighting the COVID-19 crisis. Weiss et al. have focused in detail on the antiviral efficacies of some metal nanoparticles, involving copper and silver [64]. Mechanistically, SARS-CoV might be subjected to similar antiviral activity as a role of ROS and the toxicity of Ag+ emissions of Ag-NPs to virus’s species, encompassing HIV and HBV. Briefly, it was claimed that ionic species could link to surface proteins of the virus resulting in viral damage and accumulation as well as blocking viral replication [65,66], thereby enhancing the reaction with intracellular enzymes, influenza A virus (H9N2), herpes simplex virus, and orthopoxvirus [67,68]. Although the antiviral efficacy attributed in these sheets’ virus binding and shielding potential because of their intensive edges and attaching supported by the electrostatic attractiveness between the positive charge of nucleocapsid shell of viral particles and the negative charge on the surface of GO [69,70]. Moreover, a study published recently that displayed the inactivation effect of titanium apatite filter on SARS-CoV by S protein damaging during 6 h exposure to UV light and further constricting the viral infectiousness [71]. Therefore, it demonstrated tremendously futuristic functions in advanced drug design as well as nano-based vaccines for SARS-CoV-2 control and eradication.

As demonstrated in Figure 7 and Table 2, we overview current nanoparticles that have been utilized for the treatment of COVID-19 along with highlighting their therapeutic points of intervention. Due to higher biocompatibility and water solubility, silicon nanoparticles (SiNPs) are much more applicable and approachable. SiNPs inhibit viral attachment to host cells through strong viral binding by hydrophilic or hydrophobic bonds exerting scavenger activity of the virus, for example, mesoporous-SiO2 (mSiO2) NPs [72]. A further model of this mode of action is cationic chitosan, which prevents S protein of SARS-CoV-2 binding to ACE2 receptors on the surface of host cells via the interaction of polysaccharide chain of cationic chitosan with SARS-CoV-2 S protein [73]. A new study in 2021 has suggested that the fabricated titanium oxide nanoparticles (TiO2-NPs) nanotubes have considerable in vitro inhibitory effects on SARS-CoV-2 at lower concentrations (IC50 = 568.6 ng/mL) along with weak adverse effects on the host cells, thereby they recommend the use of these interesting nanotubes in vitro and for sterilization approaches particularly in the wall coatings [74].

Figure 7 The life cycle of SARS-CoV-2 and its replication within the host cell and the therapeutic points of intervention. Viral attachment and entry through endocytosis may represent the most important point for blocking. Nanoparticles could target SARS-CoV-2 cellular entry, viral replication, and viral packaging and assembling besides their capability to act as carriers for antiviral delivery in host cells.
Figure 7

The life cycle of SARS-CoV-2 and its replication within the host cell and the therapeutic points of intervention. Viral attachment and entry through endocytosis may represent the most important point for blocking. Nanoparticles could target SARS-CoV-2 cellular entry, viral replication, and viral packaging and assembling besides their capability to act as carriers for antiviral delivery in host cells.

Table 2

Proposed mechanism of action of nanoparticles used in COVID-19 therapy

Types Examples Mechanism of action
Therapeutics Cationic carbon dots encapsulated CCM Blocking viral entry and cell attachment via altering the uniform shape of SARS-CoV-2 surface proteins
Au-NPs Blocking viral entry and cell attachment via complex with receptor binding domain (RBD) of SARS-CoV-2 than ACE2 on cell surface of the host
Ag-NPs Blocking viral entry and cell attachment via inhibiting the entry of virion inside the host by interaction with SARS-COV-2 surface
IO-NPs Blocking viral entry and cell attachment via interactions with S1-RBD) of SARS-CoV-2
Zinc oxide NPs Blocking viral entry and cell attachment via inhibition of binding of ACE2 on cell surface of the host to S-protein SARS-CoV-2
TiO2-NPs Blocking viral entry and cell attachment via inhibition of binding of ACE2 on cell surface of the host to S-protein SARS-CoV-2
Silicon NPs (SiNPs) and mSiO2 NPs Blocking viral entry and cell attachment via inhibition of binding of ACE2 on cell surface of the host to S-protein SARS-CoV-2
GO and its derivatives Blocking viral entry and cell attachment via inhibition of binding of ACE2 on cell surface of the host to S-protein SARS-CoV-2
Nanosponges Blocking viral entry and cell attachment via inhibition of binding of ACE2 on cell surface of the host to S-protein SARS-CoV-2
Au-NPs, Ag-NPs, and glutathione-capped silver sulfide nanoclusters Interfering with DNA polymerase activity of the virus leading to inhibition of viral replication
LNPs Pulmonary salinomycin delivery for preventing the viral fusion with host cell membrane and thus hindering viral entry without induction of viral infection
Ag-NPs Artemisinin and artesunate delivery for interactions between negative charges of oxygen atoms of drugs with Ag surface
Polymeric NPs Ribavirin delivery for RNA-dependent RNA polymerase (RdRp) targeting
PLGA-loaded NPs Remdesivir delivery for RdRp targeting

2.3 Nanoparticles for COVID-19 vaccines

Viruses are nanoscale objects and can thus be considered natural nanomaterials; inactivated vaccines, live attenuated vaccines, DNA-based vector vaccines are, according to this definition, nano-based technologies. Viruses and nanoparticles manipulate at the same length, and that is why vaccine development and immunoengineering approaches in nanotechnology are extremely robust. Nanoparticles, synthetic or natural, mimic the viral structural features while biotechnology, chemical biology, and nanochemistry enable the revolutionary design of next-generation vaccine technologies. A recent review has suggested that it is the ideal time for the application of novel approaches and technologies in vaccine evolutions to generate efficacious impact in various clinical phase trials for the first time [75].

Peptide-based vaccines have been regarded as the simplest form of readily designed vaccines, rapidly validated and manufactured [76]. These sorts of vaccines are fabricated either as peptides with adjuvant mixtures or peptides-loaded nanocarrier or encoding nucleic acid vaccine structures. Most of the peptide-based vaccines and peptide-based nanoparticles are evaluated by in vitro and in vivo experimental tests to extend for clinical phases testing and development especially in cancer and chronic diseases [77,78]. In addition to the peptide-based COVID-19 vaccines development, academic and industrial efforts leverage foretold B-cell and T-cell epitopes in their subunit vaccines versus SARS-CoV-2; for instance, EpiVacCorona vaccine [79] (clinical trial number NCT04780035), which has been developed by the Vektor State Research Center of Virology and Biotechnology in Russia on the basis of chemically fabricated peptide antigens of viral proteins and adsorbed on an aluminum-containing adjuvant after conjugation with a carrier protein. From our view, the use of aluminum hydroxide as an adjuvant represents a hazardous limitation in vaccine manufacture and development due to some serious endogenous signals and diseases related to the existence of excess aluminum quantities in the body.

Nanoparticles have basically offered both peptide-based vaccines-dependent factors for effectiveness, namely adjuvants and delivery systems. By engaging emerging plans for targeting cellular subsets and subcellular locations or lymph nodes, the immune profiles of nanoparticle vaccines tailored to attack specific location of diseases, and their efficacies could be ameliorated. For example, the exploitation of natural trafficking capability of albumin to lymph nodes by the state-of-the-art strategy of albumin hitchhiking [80]. Currently, nanoparticle-adjuvanted potency to address particular subsets of macrophages and lymph node-settled dendritic cells was recruited for the design and shape of a dual-targeting HBV vaccine. In a chronic HBV mouse model, the noticeable immune responses initiated via these specific subsets resulted in a stimulated activity of HBV viral clearance [81]. Vaccine design markers such as embedded antigens versus surface-presented antigens administer the presentation and processing of the antigen. Although the former demands the nanocarrier degradation or disassembly, and therefore resembles viral infection for the cellular immune response, the latter leads essentially to the humoral immune response created via the extrinsically presented viral proteins [82]. Moreover, polymeric micelle nanocarriers that switch antigenic peptides configuration to simplify cytosolic delivery could be reliably utilized for antigen-displaying cell uptake, antigen cross-presentation, and lymph nodes targeting [83].

VLPs are recent technology represented as one one of peptide-guided nanotechnologies which were generated from bacteriophages, mammalian and insect viruses for innovative applications of various immunotherapies and vaccines [84]. There is a close similarity between VLPs and diseased pathogens in the molecular and pathological behaviors for much more visible to the immune system. Furthermore, VLP delivery platforms also are of service as adjuvants for effective amplifiers and activators of the antigen-specific immune response; hence, the variety of VLP nanostructures is in the stage of development, and some of them are in the pipeline of clinical trials [85]. Subunit vaccine candidates represent minimal constructions of SARS-CoV-2, which can induce protective immune responses when codelivered with some molecular adjuvants for triggered immunogenicity. For instance, SARS-CoV-2 subunit vaccine candidates are either S1/S2 subunits or fully length S protein formulations combined with adjuvants. In May 2020, the Novavax vaccine has been developed and entered a phase I/II trial [86]. Moreover, the most outstanding examples are COVAX-19, NVX-CoV2373, and VAT00002, which have been developed by Vaxine, Novavax, and Sanofi Pasteur/GSK along with noticeable progress in clinical outcomes either in phase II or phase III [87,88]. The recombinant expression method has been used to produce VLP vaccines undergoing genetic engineering for the integration of immunomodulators, ligands, and targeting molecules. Both self-assembled VLPs and protein nanoparticles exhibit extremely monodisperse and stable vaccine platforms. Alongside the production of protein nanoparticles from subunits of antigens, their presentation and expression on proteinaceous bioengineered scaffolds, for example, encapsulin, bacteriophage, and ferritin VLPs have also been used to accomplish multivalent antigen displaying for augmented immunogenicity [75,89]. Eventually, subunit vaccines can outline the viral proteins combined with fabricated protein cages, VLPs and nano-based materials, which are recruited as delivery vehicles and/or adjuvants, plus rewarding additional benefits inveterate to every nanoplatform [90,91]. CoVLP vaccine has been regarded as one of VLPs candidates for SARS-CoV-2, passed to Phase 3 clinical trials and developed by Canada-based Medicago introducing the prefused stable nanostructure of the S protein on self-assembling VLPs surface [92].

Nucleic acid-based vaccines are a promotive substitute to traditional vaccine strategies addressed to deliver the genetic material for in situ viral proteins production. Both mRNA and DNA vaccines represent this type of category in terms of COVID-19 fighting. Although these forms of vaccines are fascinating in the range of scalability, stability, and safety, there is a higher proportion of failure for undergoing clinical trial developments as shown finally with other modern technologies [93]. The induction of both CD4+ and CD8+ T cell responses has offered the most powerful advantage of this type of vaccine for virus control and elimination [94,95]. mRNA-1273 (clinical trial number NCT04792567) and BNT162b2 (clinical trial number NCT04780659) vaccines as shown in Figure 8, are the current examples of mRNA-based technology vaccines, have been developed by Moderna and BioNTech-Pfizer pharmaceuticals, respectively [96,97]. BNT162b2 vaccine for emergency use in preventing COVID-19 infection has recently been moved to be fully approved by the FDA in USA.

Figure 8 mRNA-1273 and BNT162 vaccines for COVID-19 infection.
Figure 8

mRNA-1273 and BNT162 vaccines for COVID-19 infection.

Harnessing nanoparticle-based encapsulation in mRNA-1273 and BNT162b2 vaccines has essentially offered a critical impact on half-life prolongation and stability increment because mRNA has a very short onset duration with immunogenetic mutations [98]. Furthermore, ARCT-021 vaccine developed by Arcturus Therapeutics is a good example for shaping self-amplifying RNA technology to extend the half-life of the RNA and thereby increase S protein expression levels [99]. Nanotechnology-based trends provide extraordinary solutions for challenges related to delivery by trafficking and addressing the vaccine to proper cellular populations and subcellular sites. Although formulated nanocarriers involving polymeric nanoparticles and cationic liposomes have enormously been utilized for DNA vaccine delivery across cell membranes, targeted nanoconstructs could further boost nuclear translocation of the plasmid DNA [100].

2.3.1 Currently active and recruiting nanoparticles in clinical pipelines for COVID-19 vaccines

We are still awaiting approximately ten innovative technologies for nanoparticles in COVID-19 combating that have started since 2019. Table 3 overviews these novel nanoparticle technologies. Most of these technologies are based on protein subunits and LNPs utilized for nucleic acid-based vaccines particularly mRNA-based vaccines.

Table 3

Currently active and recruiting nanoparticles in clinical pipelines that have been used for the production of COVID-19 vaccines

Name and nanoparticles Type and payload Developer Route Dose number Clinical studies status
NVX-CoV2373 (Covovax®, Nuvaxovid®) SARS-CoV-2 rS/Matrix-M1 adjuvant Protein subunit (recombinant S protein) Novavax IM 2 (day 0 + 21) Phase 3 recruiting NCT04611802, NCT04583995, and NCT04533399
VAT00002 and VAT00008 (Vidprevtyn®) SARS-CoV-2 rS/AS03 adjuvant Protein subunit (recombinant S protein) Sanofi Pasteur & GSK IM 2 (day 0 + 21) Phase 3 recruiting NCT04904549
COVAX-19 (Spikogen®) SARS-CoV-2 rS/Advax adjuvant Protein subunit (recombinant S protein) South Australian-based biotech (Vaxine) IM 2 (day 0 + 21) Phase 1 recruiting NCT04453852
Phase 2 recruiting NCT04944368
Phase 3 recruiting NCT05005559
GBP510 Protein subunit (recombinant S protein, RBD) SK Bioscience IM 2 (day 0 + 21) Phase 1/2 recruiting NCT04742738, NCT04750343
Self-assembled protein nanoparticle immunogen Phase 3 recruiting NCT05007951
CoVLP virus like particle based on Australian weed, Nicotiana benthamiana Plant-based SARS-CoV-2 spike protein (CoVLP) Canada Medicago IM 2 (day 0 + 21) Phase 1 recruiting NCT04450004
Phase 1/2 recruiting NCT05065619
Phase 2/3 recruiting NCT04636697
Phase 3 recruiting NCT05040789
mRNA-1283 RNA-based vaccine (mRNA) ModernaTX, Inc. IM 2 (day 0 + 28) Phase 1 recruiting NCT04813796
LNPs Phase 2 recruiting NCT05137236
DS-5670a, LNPs RNA-based vaccine (mRNA) Daiichi Sankyo Co., Ltd. IM 2 (day 0 + 21) Phase 1/2 recruiting NCT04821674
CVnCoV RNA-based vaccine (mRNA) CureVac AG IM 2 (day 0 + 28) Phase 3 recruiting NCT04674189, NCT04838847, and NCT04860258
LNPs
ARCT-021/LUNAR-COVID19 RNA-based vaccine (mRNA) Arcturus therapeutics IM 2 (day 0 + 28) Phase 2 recruiting NCT04728347 and NCT04480957
Lipid-enabled nucleomonomer moiety mRNA

2.3.2 FDA approved nanoparticles for the production of COVID-19 vaccines

There are two FDA approved nano-based vaccines demonstrating the continued progress of nanoparticles to be introducing into the market and the clinic. Table 4 summarizes these approved nanoparticles by FDA for use for successful protection from COVID-19.

Table 4

Currently FDA approved nanoparticles that have been used for the production of COVID-19 vaccines

Name and nanoparticles Type and payload Developer Route Dose number Clinical studies status
mRNA-1273 (Spikevax®) LNPs RNA-based vaccine (mRNA) Moderna & National Institute of Allergy and Infectious Diseases IM 2 (day 0 + 28) Phase 1 NCT04283461
Phase 2 NCT04405076
Phase 3 NCT04470427, NCT04760132, NCT04792567, and NCT04885907
FDA, emergency use authorization (2020)
Tozinameran/BNT162b2 LNPs RNA-based vaccine (mRNA) Pfizer/BioNTech IM 2 (day 0 + 21) Phase 1/2 NCT04380701
Phase 2/3 NCT04368728
Phase 3 NCT04760132, NCT04780659, NCT04775069, NCT04852861, and NCT04878211
FDA, emergency use authorization (2020)

3 Concurrent nanomedicine challenges

Alveolar fluids and mucus may primarily constitute the main physiological barriers for reticuloendothelial and intranasal structures in systemic nanodelivery. Biodegradability and the ability to provide the preferred cell type along with persistent drug delivery are required to maximize the endogenous efficacy of nanoparticles. In addition, nanoparticles should acquire intrinsic strength for overcoming cellular degradation processes [101,102]. However, studies showed that those procedures could cause severe damage to the air locations and extensive disturbance in the functions of lung. Nanoparticles of delivery methods established showed significant potential applications. Oxidative stress, genotoxicity, fibrosis, and inflammation are four pathobiological adverse effects that should be fully considered in associated methods for the production of nanoparticle perspectives [103]. There is no evidence for achieving mucosal immunity prolongation, safety, and full protection versus the virus by whether oral or nasal nano-based vaccines. Moreover, the correlation between different administration routes of variable age groups and generation of appropriate protection is still mysterious [104,105]. Sekimukai and coauthors discussed the massively allergic inflammation, which induced failure of protein-loaded Au-NPs to boost vaccine efficacy besides the occurrence of declining eosinophilic infiltration and triggering IgG reaction [106]. However, once nano-based medicines were diluted, they would lose their efficacies due to the disassociation of the compound–virus complex leading to virus liberation and restoration of viral replication, hence hampering their clinical translation success [107,108]. Nanoparticle-induced oxidative stress is owing to cellular ROS production or interference with mitochondrial respiration leading to prospective toxicities. Several types of researches have studied the intratracheal uptake of TiO2-NPs during 90 days of administration in mice models and demonstrated remarkable antioxidant levels, ROS and inflammatory cytokines generation due to the nanoparticle accumulation in the lungs of mice along with a tremendous elevation of the AP-1 transcription factor (activator protein 1), which negatively affects the processes of transcription in the cells [109,110]. One of the harmful effects of nanoparticles is the endogenous interaction with DNA resulting in extensive genotoxicity, for example, carbon nanotubes which can cause fibrosis and pneumonia in experimental mice models, thereby it is essential to estimate such intrinsic factors before nanoparticle harnessing in clinical use [111,112]. The deep study of nanoparticle behaviors postexposure inside the human body has become a huge concern toward clinical practice. In this context, platinum-containing therapies such as cisplatin and carboplatin are among the most potent and used cancer chemotherapeutics for the treatment of several solid cancers [113]. Nephrotoxicity and off-targeting to normal tissues are major arising side effects of utilizing platinum-based therapeutic drugs [114]. Nano-based chemotherapeutics has possessed the potential tool in order to ameliorate the characterization of drug delivery as well as get rid of this challenge. However, the rapid reticuloendothelial clearance of nano-based therapeutic drugs might represent the main limitation for clinical settings, thus maximizing serious toxicities and lowering curative efficacy on off-target organs and tissues such as kidney, liver, and spleen [115–117]. In vitro and in vivo experiments of IO-NPs have exhibited ROS production as a harmful adverse reaction [118,119]. To avoid this, surface coating of IO-NPs by using inert polymers gradually recovers cell viability to be one of the available solutions for the improvement of nanoparticle deficiencies [120]. The profound level of inflammatory cytokines in the human body is generally correlated to the sharpness of several infections. The exaggerated release of these components is popularly named as cytokine storm, caused by uncontrolled reactions of our immune system as a result of severe pathogenic infections [121,122]. Macrophages and monocytes in the immune system have been regarded as a fundamental cornerstone for curbing these extensive inflammatory responses and controlling the adaptive and innate immune reactions [123]. In case of SARS-CoV-2 infection, this storm boosts the severity of symptoms in most infected patients, which mimic those that happened in macrophage stimulating syndrome incorporating with dysfunction of macrophage [124]. Immunosuppressive agents such as methylprednisolone have been prescribed as a potent treatable approach against cytokine storms in severe cases of COVID-19. The regulated modulation of factors governing innate and adaptive immune responses at COVID-19 infected patients is also recently under consideration. Unfortunately, this activation is still not adequately enough for the resultant pathological effects of cytokine storms. Targeting primary immune cells promoting cytokine storm progression through utilizing therapeutic patterns could contribute as an alternative option in terms of remedy of severe COVID-19 cases [125,126]. Earlier results have revealed that the depletion of liposome-associated macrophages might play a curative function of limiting the generation of cytokines at infectious and autoimmune diseases [127,128]. The surface functionalization with targeted ligands and peptides of nano-based therapeutics for efficient attachment to major extracellular factors of macrophage membrane with higher affinity can readily enhance their particular uptake for alleviating macrophage dysfunctional responses [129,130]. As shown in Figure 9, we summarize the major advantages and disadvantages of several nanoparticles that have substantially participated in the eradication of COVID-19 infectiousness.

Figure 9 Advantages and disadvantages of major classes of nanoparticles used for combating COVID-19 infectiousness.
Figure 9

Advantages and disadvantages of major classes of nanoparticles used for combating COVID-19 infectiousness.

4 Future outlooks

Massive advancements harnessing nanotechnology-based approaches will be fulfilled in COVID-19 diagnosis and therapy in the upcoming future. Not only exploitation of these nano-based tools in this issue, but also in a broad area of protruding pathogens. Furthermore, efficient delivery of active constituents using nano-based vaccines and monoclonal antibodies toward infected locations accelerates precise virus detection. Eventually, the capability of nanomaterials for undergoing clinical translation and enhancing their scalability in production remains a big obstacle to ongoing development and progress. Mesenchymal stem cell secretome exhibits one of the recent regenerative nanomedicine options for COVID-19. Mesenchymal stem cells play critical functions in acute respiratory distress syndrome remedy particularly against fibrosis through secretion of VEGF, hepatocyte growth factor, and IL-10 for repairing and regenerating excessive damage in the lung [131]. Moreover, these stem cells can cause inhibition of the irregular employment of macrophages and T lymphocytes, inducing their proper differentiation into anti-inflammatory macrophages and T regulatory subsets. All of these significant functions of mesenchymal stem cells enable them a great opportunity to be one of the optimum therapeutic preferences among further cellular therapeutics for COVID-19 treatment [132]. Exosomes are tiny packs, initiated by stem cells and encapsulated with nucleic acid materials and cellular proteins [133], characterized by their immune-modulatory functions, anti-inflammatory activities, and regenerative assimilation likely mimic to those of their ancestors, mesenchymal stem cells [134,135]. Consequently, exosomes have represented futuristic therapeutic regimens for COVID-19 eradication.

5 Conclusion

This review has briefly argued the COVID-19 pathophysiological causes and the role of nanomedicine approach toward its combating. We have summarized a remarkable progression of the development of nano-based diagnostic, therapies, and vaccines against COVID-19. Nanotherapeutics (nanovaccines and nanoparticle-based therapeutics), single and combined antiviral therapies along computational-based methods are innovative tracks for designing novel drug discovery for fighting COVID-19. Nanoparticles of delivery methods established showed significant potential applications. Oxidative stress, genotoxicity, fibrosis, and inflammation are four pathobiological adverse effects that should be fully considered in associated methods for the production of nanoparticle perspectives. Nanoparticle-induced oxidative stress is due to cellular ROS production or interference with mitochondrial respiration leading to prospective toxicities. One of the harmful effects of nanoparticles is the endogenous interaction with DNA resulting in extensive genotoxicity; for example, carbon nanotubes that can cause fibrosis and pneumonia in experimental mice models, thereby it is essential to estimate such intrinsic factors prior to nanoparticle harnessing in clinical use. All of these drawbacks are not neglectable in rational engineering and design, still remain unclear leading to several difficulties to accomplish an efficient clinical practice and translation. Finally, Mesenchymal stem cells and exosomes might offer promising tools for the treatment of COVID-19 in the near future.

tel: +81-52-789-4674

Acknowledgments

The authors gratefully acknowledge BioRender for supporting the design of the figures.

  1. Funding information: The authors state no funding involved.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Conflict of interest: The authors state no conflict of interest.

References

[1] Pal M, Berhanu G, Desalegn C, Kandi V. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update. Cureus. 2020;12(3):e7423.10.7759/cureus.7423Search in Google Scholar PubMed PubMed Central

[2] Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China. N Engl J Med. 2020;382(8):727–33.10.1056/NEJMoa2001017Search in Google Scholar PubMed PubMed Central

[3] Chen J, Qi T, Liu L, Ling Y, Qian Z, Li T, et al. Clinical progression of patients with COVID-19 in Shanghai. China. J Infect. 2020;80(5):e1–6.10.1016/j.jinf.2020.03.004Search in Google Scholar PubMed PubMed Central

[4] Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536–44.10.1038/s41564-020-0695-zSearch in Google Scholar PubMed PubMed Central

[5] Johansson MA, Quandelacy TM, Kada S, Prasad PV, Steele M, Brooks TJ, et al. SARS-CoV-2 transmission from people without COVID-19 symptoms. JAMA Netw Open. 2021;4(1):e2035057.10.1001/jamanetworkopen.2020.35057Search in Google Scholar PubMed PubMed Central

[6] V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19(3):155–70.10.1038/s41579-020-00468-6Search in Google Scholar PubMed PubMed Central

[7] Ke Z, Oton J, Qu K, Cortese M, Zila V, McKeane L, et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature. 2020;588(7838):498–502.10.1038/s41586-020-2665-2Search in Google Scholar PubMed PubMed Central

[8] Chatterjee M, van Putten JPM, Strijbis K. Defensive properties of mucin glycoproteins during respiratory infections-relevance for SARS-CoV-2. mBio. 2020;11(6):e02374-20.10.1128/mBio.02374-20Search in Google Scholar PubMed PubMed Central

[9] Laporte M, Raeymaekers V, Van Berwaer R, Vandeput J, Marchand-Casas I, Thibaut HJ, et al. The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways. PLoS Pathog. 2021;17(4):e1009500.10.1371/journal.ppat.1009500Search in Google Scholar PubMed PubMed Central

[10] Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol. 2021;21(2):73–82.10.1038/s41577-020-00480-0Search in Google Scholar PubMed PubMed Central

[11] Lu S, Ye Q, Singh D, Cao Y, Diedrich JK, Yates JR, et al. The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nat Commun. 2021;12(1):502.10.1038/s41467-020-20768-ySearch in Google Scholar PubMed PubMed Central

[12] Cubuk J, Alston JJ, Incicco JJ, Singh S, Stuchell-Brereton MD, Ward MD, et al. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nat Commun. 2021;12(1):1936.10.1038/s41467-021-21953-3Search in Google Scholar PubMed PubMed Central

[13] Bai Z, Cao Y, Liu W, Li J. The SARS-CoV-2 nucleocapsid protein and its role in viral structure, biological functions, and a potential target for drug or vaccine mitigation. Viruses. 2021;13(6):1115.10.3390/v13061115Search in Google Scholar PubMed PubMed Central

[14] Zhang Q, Xiang R, Huo S, Zhou Y, Jiang S, Wang Q, et al. Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Sig Transduct Target Ther. 2021;6(1):233.10.1038/s41392-021-00653-wSearch in Google Scholar PubMed PubMed Central

[15] Wang R, Chen J, Gao K, Hozumi Y, Yin C, Wei GW. Analysis of SARS-CoV-2 mutations in the united states suggests presence of four substrains and novel variants. commun. Biol. 2021;4(1):228.10.1038/s42003-021-01754-6Search in Google Scholar

[16] Müller H, Fehling SK, Dorna J, Urbanowicz RA, Oestereich L, Krebs Y, et al. Adjuvant formulated virus-like particles expressing native-like forms of the lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity. NPJ Vaccines. 2020;5(1):71.10.1038/s41541-020-00219-xSearch in Google Scholar PubMed PubMed Central

[17] Nooraei S, Bahrulolum H, Hoseini ZS, Katalani C, Hajizade A, Easton AJ, et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnol. 2021;19(1):59.10.1186/s12951-021-00806-7Search in Google Scholar PubMed PubMed Central

[18] Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583(7816):459–68.10.1038/s41586-020-2286-9Search in Google Scholar PubMed PubMed Central

[19] Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41(9):1141–9.10.1038/s41401-020-0485-4Search in Google Scholar PubMed PubMed Central

[20] Park SH, Siddiqi H, Castro DV, De Angelis AA, Oom AL, Stoneham CA, et al. Interactions of SARS-CoV-2 envelope protein with amilorides correlate with antiviral activity. PLoS Pathog. 2021;17(5):e1009519.10.1371/journal.ppat.1009519Search in Google Scholar PubMed PubMed Central

[21] Peng F, Tu L, Yang Y, Hu P, Wang R, Hu Q, et al. Management and treatment of COVID-19: the chinese experience. Can J Cardiol. 2020;3(6):915–30.10.1016/j.cjca.2020.04.010Search in Google Scholar PubMed PubMed Central

[22] Hanafy NAN, El-Kemary MA. Silymarin/curcumin loaded albumin nanoparticles coated by chitosan as muco-inhalable delivery system observing anti-inflammatory and anti COVID-19 characterizations in oleic acid triggered lung injury and in vitro COVID-19 experiment. Int J Biol Macromol. 2021;198:101–10.10.1016/j.ijbiomac.2021.12.073Search in Google Scholar PubMed PubMed Central

[23] JooJ. Diagnostic and therapeutic nanomedicine. Adv Exp Med Biol. 2021;1310(1):401–47.10.1007/978-981-33-6064-8_15Search in Google Scholar PubMed

[24] Russo E, Spallarossa A, Tasso B, Villa C, Brullo C. Nanotechnology of tyrosine kinase inhibitors in cancer therapy: A perspective. Int J Mol Sci. 2021;22(12):6538.10.3390/ijms22126538Search in Google Scholar PubMed PubMed Central

[25] Ruiz-Hitzky E, Darder M, Wicklein B, Ruiz-Garcia C, Martín-Sampedro R, Del Real G, et al. Nanotechnology responses to COVID-19. Adv Healthc Mater. 2020;9(19):e2000979.10.1002/adhm.202000979Search in Google Scholar PubMed

[26] The Cellex qSARS-CoV-2 IgG/IgM Rapid Test https://www.fda.gov/media/136625/136625/download (2020).Search in Google Scholar

[27] Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in false-Negative rate of reverse transcriptase polymerase chain reaction-Based SARS-CoV-2 tests by time since exposure. Ann Intern Med. 2020;173(4):262–7.10.7326/M20-1495Search in Google Scholar PubMed PubMed Central

[28] Afzal A. Molecular diagnostic technologies for COVID-19: limitations and challenges. J Adv Res. 2020;26(1):149–59.10.1016/j.jare.2020.08.002Search in Google Scholar PubMed PubMed Central

[29] Gorshkov K, Susumu K, Chen J, Xu M, Pradhan M, Zhu W, et al. Quantum dot-Conjugated SARS-CoV-2 spike pseudo-Virions enable tracking of angiotensin converting enzyme 2 binding and endocytosis. ACS Nano. 2020;14(9):12234–47.10.1021/acsnano.0c05975Search in Google Scholar PubMed PubMed Central

[30] Udugama B, Kadhiresan P, Kozlowski HN, Malekjahani A, Osborne M, Li VYC, et al. Diagnosing COVID-19: the disease and tools for detection. ACS Nano. 2020;14(4):3822–35.10.1021/acsnano.0c02624Search in Google Scholar PubMed PubMed Central

[31] Cho SY, Jin X, Gong X, Yang S, Cui J, Strano MS. Antibody-Free rapid detection of SARS-CoV-2 proteins using corona phase molecular recognition to accelerate development time. Anal Chem. 2021;93(44):14685–93.10.1021/acs.analchem.1c02889Search in Google Scholar PubMed PubMed Central

[32] Dzimianski JV, Lorig-Roach N, O’Rourke SM, Alexander DL, Kimmey JM, DuBois RM. Rapid and sensitive detection of SARS-CoV-2 antibodies by biolayer interferometry. Sci Rep. 2020;10(1):21738.10.1038/s41598-020-78895-xSearch in Google Scholar PubMed PubMed Central

[33] Huang C, Wen T, Shi FJ, Zeng XY, Jiao YJ. Rapid detection of igM antibodies against the SARS-CoV-2 virus via colloidal gold nanoparticle-Based lateral-Flow assay. ACS Omega. 2020;5(21):12550–6.10.1021/acsomega.0c01554Search in Google Scholar PubMed PubMed Central

[34] Qiu G, Gai Z, Tao Y, Schmitt J, Kullak-Ublick GA, Wang J. Dual-functional plasmonic photothermal biosensors for highly accurate severe acute respiratory syndrome coronavirus 2 detection. ACS Nano. 2020;14(5):5268–77.10.1021/acsnano.0c02439Search in Google Scholar PubMed PubMed Central

[35] Ali A, Shah T, Ullah R, Zhou P, Guo M, Ovais M, et al. Review on recent progress in magnetic nanoparticles: synthesis, characterization, and diverse applications. Front Chem. 2021;9(1):629054.10.3389/fchem.2021.629054Search in Google Scholar PubMed PubMed Central

[36] Vahedifard F, Chakravarthy K. Nanomedicine for COVID-19: the role of nanotechnology in the treatment and diagnosis of COVID-19. Emergent Mater. 2021;4(1):75–99.10.1007/s42247-021-00168-8Search in Google Scholar PubMed PubMed Central

[37] Dheyab MA, Khaniabadi PM, Aziz AA, Jameel MS, Mehrdel B, Oglat AA, et al. Focused role of nanoparticles against COVID-19: diagnosis and treatment. Photodiagnosis Photodyn Ther. 2021;34(1):102287.10.1016/j.pdpdt.2021.102287Search in Google Scholar PubMed PubMed Central

[38] Wang M, Fu A, Hu B, Tong Y, Liu R, Liu Z, et al. Nanopore targeted sequencing for the accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses. Small. 2020;16(32):e2002169.10.1002/smll.202002169Search in Google Scholar PubMed PubMed Central

[39] Njoki PN, Jacob A, Khan B, Luo J, Zhong CJ. Formation of gold nanoparticles catalyzed by platinum nanoparticles: assessment of the catalytic mechanism. J Phys Chem B. 2006;110(45):22503–9.10.1021/jp0642342Search in Google Scholar PubMed

[40] Alafeef M, Moitra P, Dighe K, Pan D. RNA-extraction-free nano-amplified colorimetric test for point-of-care clinical diagnosis of COVID-19. Nat Protoc. 2021;16(6):3141–62.10.1038/s41596-021-00546-wSearch in Google Scholar PubMed

[41] Shrivastav AM, Cvelbar U, Abdulhalim I. A comprehensive review on plasmonic-based biosensors used in viral diagnostics. Commun Biol. 2021;4(1):70.10.1038/s42003-020-01615-8Search in Google Scholar PubMed PubMed Central

[42] Chacón-Torres JC, Reinoso C, Navas-León DG, Briceño S, González G. Optimized and scalable synthesis of magnetic nanoparticles for RNA extraction in response to developing countries’ needs in the detection and control of SARS-CoV-2. Sci Rep. 2020;10(1):19004.10.1038/s41598-020-75798-9Search in Google Scholar PubMed PubMed Central

[43] Carter LJ, Garner LV, Smoot JW, Li Y, Zhou Q, Saveson CJ, et al. Assay techniques and test development for COVID-19 diagnosis. ACS Cent Sci. 2020;6(5):591–605.10.1021/acscentsci.0c00501Search in Google Scholar PubMed PubMed Central

[44] Zhu X, Wang X, Han L, Chen T, Wang L, Li H, et al. Multiplex reverse transcription loop-mediated isothermal amplification combined with nanoparticle-based lateral flow biosensor for the diagnosis of COVID-19. Biosens Bioelectron. 2020;166(1):112437.10.1016/j.bios.2020.112437Search in Google Scholar PubMed PubMed Central

[45] Mertens P, De Vos N, Martiny D, Jassoy C, Mirazimi A, Cuypers L, et al. Development and potential usefulness of the COVID-19 ag respi-Strip diagnostic assay in a pandemic context. Front Med. 2020;7(1):225.10.3389/fmed.2020.00225Search in Google Scholar PubMed PubMed Central

[46] Mahmoudi M. Emerging biomolecular testing to assess the risk of mortality from COVID-19 infection. Mol Pharm. 2021;18(2):476–82.10.1021/acs.molpharmaceut.0c00371Search in Google Scholar PubMed PubMed Central

[47] Kalantar-Zadeh K, Ward SA, Kalantar-Zadeh K, El-Omar EM. Considering the effects of microbiome and diet on SARS-CoV-2 infection: nanotechnology roles. ACS Nano. 2020;14(5):5179–82.10.1021/acsnano.0c03402Search in Google Scholar PubMed PubMed Central

[48] Pindiprolu SK, Kumar CS, Golla VS, Likitha P, Chandra S, Ramachandra RK. Pulmonary delivery of nanostructured lipid carriers for effective repurposing of salinomycin as an antiviral agent. Med hypotheses. 2020;143(1):109858.10.1016/j.mehy.2020.109858Search in Google Scholar PubMed PubMed Central

[49] Ianevski A, Yao R, Fenstad MH, Biza S, Zusinaite E, Reisberg T, et al. Potential antiviral options against SARS-CoV-2 infection. Viruses. 2020;12(6):642.10.3390/v12060642Search in Google Scholar PubMed PubMed Central

[50] Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res. 2020;178(1):104792.10.1016/j.antiviral.2020.104792Search in Google Scholar PubMed PubMed Central

[51] Pindiprolu SKSS, Pindiprolu SH. Plausible mechanisms of niclosamide as an antiviral agent against COVID-19. Med Hypotheses. 2020;140(1):109765.10.1016/j.mehy.2020.109765Search in Google Scholar PubMed PubMed Central

[52] Nasrollahzadeh M, Sajjadi M, Soufi GJ, Iravani S, Varma RS. Nanomaterials and nanotechnology-Associated innovations against viral infections with a focus on coronaviruses. Nanomaterials. 2020;10(6):1072.10.3390/nano10061072Search in Google Scholar PubMed PubMed Central

[53] Zhang Q, Honko A, Zhou J, Gong H, Downs SN, Vasquez JH, et al. Cellular nanosponges inhibit SARS-CoV-2 infectivity. Nano Lett. 2020;20(7):5570–4.10.1021/acs.nanolett.0c02278Search in Google Scholar PubMed PubMed Central

[54] Ting D, Dong N, Fang L, Lu J, Bi J, Xiao S, et al. Multisite inhibitors for enteric coronavirus: antiviral cationic carbon dots based on curcumin. ACS Applied Nano Materials. 2018;1(10):5451–9.10.1021/acsanm.8b00779Search in Google Scholar

[55] Florindo HF, Kleiner R, Vaskovich-Koubi D, Acúrcio RC, Carreira B, Yeini E, et al. Immune-mediated approaches against COVID-19. Nat Nanotechnol. 2020;15(8):630–45.10.1038/s41565-020-0732-3Search in Google Scholar PubMed PubMed Central

[56] Liao MT, Wu CC, Wu SV, Lee MC, Hu WC, Tsai KW, et al. Resveratrol as an adjunctive therapy for excessive oxidative stress in aging COVID-19 patients. Antioxidants. 2021;10(9):1440.10.3390/antiox10091440Search in Google Scholar PubMed PubMed Central

[57] Du T, Liang J, Dong N, Lu J, Fu Y, Fang L, et al. Glutathione-capped ag2S nanoclusters inhibit coronavirus proliferation through blockage of viral RNA synthesis and budding. ACS Appl Mater Interfaces. 2018;10(5):4369–78.10.1021/acsami.7b13811Search in Google Scholar PubMed

[58] Chen YN, Hsueh YH, Hsieh CT, Tzou DY, Chang PL. Antiviral activity of graphene-silver nanocomposites against non-Enveloped and enveloped viruses. Int J Environ Res Public Health. 2016;13(4):430.10.3390/ijerph13040430Search in Google Scholar PubMed PubMed Central

[59] León-Buitimea A, Garza-Cárdenas CR, Garza-Cervantes JA, Lerma-Escalera JA, Morones-Ramírez JR. The demand for new antibiotics: antimicrobial peptides, nanoparticles, and combinatorial therapies as future strategies in antibacterial agent design. Front Microbiol. 2020;11(1):1669.10.3389/fmicb.2020.01669Search in Google Scholar PubMed PubMed Central

[60] Jazie AA, Albaaji AJ, Abed SA. A review on recent trends of antiviral nanoparticles and airborne filters: special insight on COVID-19 virus. Air Qual Atmos Health. 2021;1(1):1–14.10.1007/s11869-021-01055-1Search in Google Scholar PubMed PubMed Central

[61] Ansari MA, Almatroudi A, Alzohairy MA, AlYahya S, Alomary MN, Al-Dossary HA, et al. Lipid-based nano delivery of tat-peptide conjugated drug or vaccine-promising therapeutic strategy for SARS-CoV-2 treatment. Expert Opin Drug Deliv. 2020;17(12):1671–4.10.1080/17425247.2020.1813712Search in Google Scholar PubMed PubMed Central

[62] Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis. 2020;11(2):216–28.10.14336/AD.2020.0228Search in Google Scholar PubMed PubMed Central

[63] PinkyGupta, S, Krishnakumar V, Sharma Y, Dinda AK, Mohanty S. Mesenchymal stem cell derived exosomes: a nano platform for therapeutics and drug delivery in combating COVID-19. Stem Cell Rev Rep. 2021;17(1):33–43.10.1007/s12015-020-10002-zSearch in Google Scholar PubMed PubMed Central

[64] Weiss C, Carriere M, Fusco L, Capua I, Regla-Nava JA, Pasquali M, et al. Toward nanotechnology-Enabled approaches against the COVID-19 pandemic. ACS Nano. 2020;14(6):6383–406.10.1021/acsnano.0c03697Search in Google Scholar PubMed PubMed Central

[65] Imani SM, Ladouceur L, Marshall T, Maclachlan R, Soleymani L, Didar TF. Antimicrobial nanomaterials and coatings: current mechanisms and future perspectives to control the spread of viruses including SARS-CoV-2. ACS Nano. 2020;14(10):12341–69.10.1021/acsnano.0c05937Search in Google Scholar PubMed PubMed Central

[66] Chue-Gonçalves M, Pereira GN, Faccin-Galhardi LC, Kobayashi RKT, Nakazato G. Metal nanoparticles against viruses: possibilities to fight SARS-CoV-2. Nanomaterials. 2021;11(11):3118.10.3390/nano11113118Search in Google Scholar PubMed PubMed Central

[67] Medhi R, Srinoi P, Ngo N, Tran HV, Lee TR. Nanoparticle-based strategies to combat COVID-19. ACS Appl Nano Mater. 2020;3(9):8557–80.10.1021/acsanm.0c01978Search in Google Scholar

[68] Seifi T, Reza, Kamali A. Antiviral performance of graphene-based materials with emphasis on COVID-19: A review. Med Drug Discov. 2021;11(1):100099.10.1016/j.medidd.2021.100099Search in Google Scholar PubMed PubMed Central

[69] Innocenzi P, Stagi L. Carbon-based antiviral nanomaterials: graphene, C-dots, and fullerenes. A perspective. Chem Sci. 2020;11(26):6606–22.10.1039/D0SC02658ASearch in Google Scholar

[70] Palmieri V, Papi M. Can graphene take part in the fight against COVID-19? Nano Today. 2020;33(1):100883.10.1016/j.nantod.2020.100883Search in Google Scholar PubMed PubMed Central

[71] Khaiboullina S, Uppal T, Dhabarde N, Subramanian VR, Verma SC. Inactivation of human coronavirus by titania nanoparticle coatings and UVC radiation: throwing light on SARS-CoV-2. Viruses. 2020;13(1):19.10.3390/v13010019Search in Google Scholar PubMed PubMed Central

[72] Chintagunta AD, M SK, Nalluru S, Ns SK. Nanotechnology: an emerging approach to combat COVID-19. Emergent Mater. 2021;4(1):1–12.10.1007/s42247-021-00178-6Search in Google Scholar PubMed PubMed Central

[73] Iravani S, Varma RS. Important roles of oligo-and polysaccharides against SARS-CoV-2: recent advances. Appl Sci. 2021;11(8):3512.10.3390/app11083512Search in Google Scholar

[74] Hamza RZ, Gobouri AA, Al-Yasi HM, Al-Talhi TA, El-Megharbel SM. A new sterilization strategy using tiO2 nanotubes for production of free radicals that eliminate viruses and application of a treatment strategy to combat infections caused by emerging SARS-CoV-2 during the COVID-19 pandemic. Coatings. 2021;11(6):680.10.3390/coatings11060680Search in Google Scholar

[75] Shin MD, Shukla S, Chung YH, Beiss V, Chan SK, Ortega-Rivera OA, et al. COVID-19 vaccine development and a potential nanomaterial path forward. Nat Nanotechnol. 2020;15(8):646–55.10.1038/s41565-020-0737-ySearch in Google Scholar PubMed

[76] Di Natale C, La Manna S, De Benedictis I, Brandi P, Marasco D. Perspectives in peptide-based vaccination strategies for syndrome coronavirus 2 pandemic. Front Pharmacol. 2020;11(1):578382.10.3389/fphar.2020.578382Search in Google Scholar PubMed PubMed Central

[77] Nelde A, Rammensee HG, Walz JS. The peptide vaccine of the future. Mol Cell Proteomics. 2021;20(1):100022.10.1074/mcp.R120.002309Search in Google Scholar PubMed PubMed Central

[78] Tornesello AL, Tagliamonte M, Tornesello ML, Buonaguro FM, Buonaguro L. Nanoparticles to improve the efficacy of peptide-Based cancer vaccines. Cancers. 2020;12(4):1049.10.3390/cancers12041049Search in Google Scholar PubMed PubMed Central

[79] Ryzhikov AB, Ryzhikov EA, Bogryantseva MP, Usova SV, Danilenko ED, Nechaeva EA, et al. The “EpiVacCorona” vaccine for the prevention of COVID-19, in volunteers aged 18–60 years (phase I–II). Russ J Infect Immunity. 2021;11(2):283–96.10.15789/2220-7619-ASB-1699Search in Google Scholar

[80] Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2021;20(2):101–24.10.1038/s41573-020-0090-8Search in Google Scholar PubMed PubMed Central

[81] Wang W, Zhou X, Bian Y, Wang S, Chai Q, Guo Z, et al. Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B. Nat Nanotechnol. 2020;15(5):406–16.10.1038/s41565-020-0648-ySearch in Google Scholar PubMed PubMed Central

[82] Ueda G, Antanasijevic A, Fallas JA, Sheffler W, Copps J, Ellis D, et al. Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens. Elife. 2020;9(1):e57659.10.7554/eLife.57659Search in Google Scholar PubMed PubMed Central

[83] Wang L, Wang Z, Qin Y, Liang W. Delivered antigen peptides to resident CD8α + DCs in lymph node by micelle-based vaccine augment antigen-specific CD8 + effector T cell response. Eur J Pharm Biopharm. 2020;147(1):76–86.10.1016/j.ejpb.2019.12.013Search in Google Scholar PubMed

[84] Zepeda-Cervantes J, Ramírez-Jarquín JO, Vaca L. Interaction between virus-Like particles (VLPs) and pattern recognition receptors (PRRs) from dendritic cells (DCs): toward better engineering of VLPs. Front Immunol. 2020;11(1):1100.10.3389/fimmu.2020.01100Search in Google Scholar PubMed PubMed Central

[85] Cappellano G, Abreu H, Casale C, Dianzani U, Chiocchetti A. Nano-Microparticle platforms in developing next-Generation vaccines. Vaccines. 2021;9(6):606.10.3390/vaccines9060606Search in Google Scholar PubMed PubMed Central

[86] https://www.globenewswire.com/news-release/2020/05/25/2038259/0/en/Novavax-initiates-Phase-1-2-Clinical-Trial-of-COVID-19-Vaccine. (2020).Search in Google Scholar

[87] https://www.who.int/news/item/18-12-2020-covax-announces-additional-deals-to-access-promising-covid-19-vaccine-candidates-plans-global-rollout-starting-q1-2021 (2020).Search in Google Scholar

[88] https://www.genengnews.com/news/sanofi-gsk-launch-phase-ii-trial-of-refined-covid-19-vaccine/ (2021).Search in Google Scholar

[89] Le DT, Müller KM. In vitro assembly of virus-Like particles and their applications. Life. 2021;11(4):334.10.3390/life11040334Search in Google Scholar PubMed PubMed Central

[90] Akbay B, Abidi SH, Ibrahim MAA, Mukhatayev Z, Ali S. Multi-Subunit SARS-CoV-2 vaccine design using evolutionarily conserved T- and B- cell epitopes. Vaccines. 2021;9(7):702.10.3390/vaccines9070702Search in Google Scholar PubMed PubMed Central

[91] Hillebrandt N, Vormittag P, Bluthardt N, Dietrich A, Hubbuch J. Integrated process for capture and purification of virus-Like particles: enhancing process performance by cross-flow filtration. Front Bioeng Biotechnol. 2020;8(1):489.10.3389/fbioe.2020.00489Search in Google Scholar PubMed PubMed Central

[92] Ward BJ, Gobeil P, Séguin A, Atkins J, Boulay I, Charbonneau PY, et al. Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19. Nat Med. 2021;27(6):1071–8.10.1038/s41591-021-01370-1Search in Google Scholar PubMed PubMed Central

[93] Heine A, Juranek S, Brossart P. Clinical and immunological effects of mRNA vaccines in malignant diseases. Mol Cancer. 2021;20(1):52.10.1186/s12943-021-01339-1Search in Google Scholar PubMed PubMed Central

[94] Sadarangani M, Marchant A, Kollmann TR. Immunological mechanisms of vaccine-induced protection against COVID-19 in humans. Nat Rev Immunol. 2021;21(8):475–84.10.1038/s41577-021-00578-zSearch in Google Scholar PubMed PubMed Central

[95] Smith TRF, Patel A, Ramos S, Elwood D, Zhu X, Yan J, et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Nat Commun. 2020;11(1):2601.10.1038/s41467-020-16505-0Search in Google Scholar PubMed PubMed Central

[96] Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA vaccine against SARS-CoV-2—preliminary report. N Engl J Med. 2020;383(20):1920–31.10.1056/NEJMoa2022483Search in Google Scholar PubMed PubMed Central

[97] BioNTech and Pfzer announce regulatory approval from German authority Paul-Ehrlich-Institut to commence frst clinical trial of COVID-19 vaccine candidates. BIONTECH https://investors.biontech.de/news-releases/news-release-details/biontech-and-pfzer-announce-regulatory-approval-german (2020).Search in Google Scholar

[98] Zeng C, Hou X, Yan J, Zhang C, Li W, Zhao W, et al. Leveraging mRNA sequences and nanoparticles to deliver SARS-CoV-2 antigens in vivo. Adv Mater. 2020;32(40):e2004452.10.1002/adma.202004452Search in Google Scholar PubMed PubMed Central

[99] Arcturus Therapeutics and Duke-NUS Medical School Partner to Develop a Coronavirus (COVID-19) Vaccine using STARR™ Technology https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-and-duke-nus-medical-school-partner (2020).Search in Google Scholar

[100] Lim M, Badruddoza AZM, Firdous J, Azad M, Mannan A, Al-Hilal TA, et al. Engineered nanodelivery systems to improve DNA vaccine technologies. Pharmaceutics. 2020;12(1):30.10.3390/pharmaceutics12010030Search in Google Scholar PubMed PubMed Central

[101] Varahachalam SP, Lahooti B, Chamaneh M, Bagchi S, Chhibber T, Morris K, et al. Nanomedicine for the SARS-CoV-2: state-of-the-art and future prospects. Int J Nanomedicine. 2021;16(1):539.10.2147/IJN.S283686Search in Google Scholar PubMed PubMed Central

[102] Gagliardi A, Giuliano E, Venkateswararao E, Fresta M, Bulotta S, Awasthi V, et al. Biodegradable polymeric nanoparticles for drug delivery to solid tumors. Front Pharmacol. 2021;12(1):601626.10.3389/fphar.2021.601626Search in Google Scholar PubMed PubMed Central

[103] Tirumala MG, Anchi P, Raja S, Rachamalla M, Godugu C. Novel methods and approaches for safety evaluation of nanoparticle formulations: A focus towards in vitro models and adverse outcome pathways. Front Pharmacol. 2021;12(1):612659.10.3389/fphar.2021.612659Search in Google Scholar PubMed PubMed Central

[104] Lavelle EC, Ward RW. Mucosal vaccines - fortifying the frontiers. Nat Rev Immunol. 2021;26(1):1–15.10.1038/s41577-021-00583-2Search in Google Scholar PubMed PubMed Central

[105] Zenobia C, Herpoldt KL, Freire M. Is the oral microbiome a source to enhance mucosal immunity against infectious diseases? NPJ Vaccines. 2021;6(1):80.10.1038/s41541-021-00341-4Search in Google Scholar PubMed PubMed Central

[106] Sekimukai H, Iwata-Yoshikawa N, Fukushi S, Tani H, Kataoka M, Suzuki T, et al. Gold nanoparticle-adjuvanted S protein induces a strong antigen-specific igG response against severe acute respiratory syndrome-related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs. Microbiol Immunol. 2020;64(1):33–51.10.1111/1348-0421.12754Search in Google Scholar PubMed PubMed Central

[107] Asdaq SM, Ikbal AM, Sahu RK, Bhattacharjee B, Paul T, Deka B, et al. Nanotechnology integration for SARS-CoV-2 diagnosis and treatment: an approach to preventing pandemic. Nanomaterials. 2021;11(7):1841.10.3390/nano11071841Search in Google Scholar PubMed PubMed Central

[108] Campos EV, Pereira AE, De Oliveira JL, Carvalho LB, Guilger-Casagrande M, De Lima R, et al. How can nanotechnology help to combat COVID-19? opportunities and urgent need. J Nanobiotechnology. 2020;18(1):1–23.10.1186/s12951-020-00685-4Search in Google Scholar PubMed PubMed Central

[109] Cheng Y, Chen Z, Yang S, Liu T, Yin L, Pu Y, et al. Nanomaterials-induced toxicity on cardiac myocytes and tissues, and emerging toxicity assessment techniques. Sci Total Environ. 2021;800(1):149584.10.1016/j.scitotenv.2021.149584Search in Google Scholar PubMed

[110] Baranowska-Wójcik E, Szwajgier D, Oleszczuk P, Winiarska-Mieczan A. Effects of titanium dioxide nanoparticles exposure on human health-a review. Biol Trace Elem Res. 2020;193(1):118–29.10.1007/s12011-019-01706-6Search in Google Scholar PubMed PubMed Central

[111] Yetisgin AA, Cetinel S, Zuvin M, Kosar A, Kutlu O. Therapeutic nanoparticles and their targeted delivery applications. Molecules. 2020;25(9):2193.10.3390/molecules25092193Search in Google Scholar PubMed PubMed Central

[112] Banavar S, Deshpande A, Sur S, Andreescu S. Ceria nanoparticle Theranostics: Harnessing Antioxidant Properties in Biomedicine and Beyond. J Phys Mater. 2021;4(1):042003.10.1088/2515-7639/ac0594Search in Google Scholar

[113] Rottenberg S, Disler C, Perego P. The rediscovery of platinum-based cancer therapy. Nat Rev Cancer. 2021;21(1):37–50.10.1038/s41568-020-00308-ySearch in Google Scholar PubMed

[114] Zhang M, Liang J, Yang Y, Liang H, Jia H, Li D. Current trends of targeted drug delivery for oral cancer therapy. Front Bioeng Biotechnol. 2020;8(1):1417.10.3389/fbioe.2020.618931Search in Google Scholar PubMed PubMed Central

[115] Pandian SR, Panneerselvam T, Pavadai P, Govindaraj S, Ravishankar V, Palanisamy P, et al. Nano based approach for the treatment of neglected tropical diseases. Front Nanotechnol. 2021;3(1):49.10.3389/fnano.2021.665274Search in Google Scholar

[116] Cheng Z, Li M, Dey R, Chen Y. Nanomaterials for cancer therapy: current progress and perspectives. J Hematol Oncol. 2021;14(1):85.10.1186/s13045-021-01096-0Search in Google Scholar PubMed PubMed Central

[117] Ulldemolins A, Seras-Franzoso J, Andrade F, Rafael D, Abasolo I, Gener P, et al. Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics. Cancer Drug Resist. 2021;4(1):44–68.10.20517/cdr.2020.59Search in Google Scholar PubMed PubMed Central

[118] Hwang YH, Kim YJ, Lee DY. Hepatic and renal cellular cytotoxic effects of heparin-coated superparamagnetic iron oxide nanoparticles. Biomater Res. 2021;25(1):36.10.1186/s40824-021-00241-7Search in Google Scholar PubMed PubMed Central

[119] Yu S, Zhang H, Zhang S, Zhong M, Fan H. Ferrite nanoparticles-Based reactive oxygen species-Mediated cancer therapy. Front Chem. 2021;9(1):184.10.3389/fchem.2021.651053Search in Google Scholar PubMed PubMed Central

[120] Ezealigo US, Ezealigo BN, Aisida SO, Ezema FI. Iron oxide nanoparticles in biological systems: antibacterial and toxicology perspective. JCIS Open. 2021;4(1):100027.10.1016/j.jciso.2021.100027Search in Google Scholar

[121] Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141–54.10.1038/s41579-020-00459-7Search in Google Scholar PubMed PubMed Central

[122] Jin Y, Ji W, Yang H, Chen S, Zhang W, Duan G. Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. Signal Transduct Target Ther. 2020;5(1):293.10.1038/s41392-020-00454-7Search in Google Scholar PubMed PubMed Central

[123] Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20(6):375–88.10.1038/s41577-020-0285-6Search in Google Scholar PubMed PubMed Central

[124] Gustine JN, Jones D. Immunopathology of hyperinflammation in COVID-19. Am J Pathol. 2021;191(1):4–17.10.1016/j.ajpath.2020.08.009Search in Google Scholar PubMed PubMed Central

[125] Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363–74.10.1038/s41577-020-0311-8Search in Google Scholar PubMed PubMed Central

[126] Yang L, Xie X, Tu Z, Fu J, Xu D, Zhou Y. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther. 2021;6(1):255.10.1038/s41392-021-00679-0Search in Google Scholar PubMed PubMed Central

[127] Kucuksezer UC, Aktas Cetin E, Esen F, Tahralı İ, Akdeniz N, Gelmez YM, et al. The role of natural killer cells in autoimmune diseases. Front Immunol. 2021;12(1):79.10.3389/fimmu.2021.622306Search in Google Scholar PubMed PubMed Central

[128] Liu J, Wan M, Lyon CJ, Hu TY. Nanomedicine therapies modulating macrophage dysfunction: a potential strategy to attenuate cytokine storms in severe infections. Theranostics. 2020;10(21):9591–600.10.7150/thno.47982Search in Google Scholar PubMed PubMed Central

[129] Izci M, Maksoudian C, Manshian BB, Soenen SJ. The use of alternative strategies for enhanced nanoparticle delivery to solid tumors. Chem Rev. 2021;121(3):1746–803.10.1021/acs.chemrev.0c00779Search in Google Scholar PubMed PubMed Central

[130] Sanità G, Carrese B, Lamberti A. Nanoparticle surface functionalization: how to improve biocompatibility and cellular internalization. Front Mol Biosci. 2020;7(1):587012.10.3389/fmolb.2020.587012Search in Google Scholar PubMed PubMed Central

[131] Bari E, Ferrarotti I, Saracino L, Perteghella S, Torre ML, Richeldi L, et al. Mesenchymal stromal cell secretome for post-COVID-19 pulmonary fibrosis: a new therapy to treat the long-term lung sequelae? Cells. 2021;10(5):1203.10.3390/cells10051203Search in Google Scholar PubMed PubMed Central

[132] Negi N, Griffin MD. Effects of mesenchymal stromal cells on regulatory T cells: current understanding and clinical relevance. Stem Cells. 2020;38(5):596–605.10.1002/stem.3151Search in Google Scholar PubMed PubMed Central

[133] Rezakhani L, Kelishadrokhi AF, Soleimanizadeh A, Rahmati S. Mesenchymal stem cell (MSC)-derived exosomes as a cell-free therapy for patients infected with COVID-19: real opportunities and range of promises. Chem Phys Lipids. 2021;234(1):105009.10.1016/j.chemphyslip.2020.105009Search in Google Scholar PubMed PubMed Central

[134] Gupta A, Kashte S, Gupta M, Rodriguez HC, Gautam SS, Kadam S. Mesenchymal stem cells and exosome therapy for COVID-19: current status and future perspective. Hum Cell. 2020;33(4):907–18.10.1007/s13577-020-00407-wSearch in Google Scholar PubMed PubMed Central

[135] Liu Q, Li S, Dupuy A, Mai HL, Sailliet N, Logé C, et al. Exosomes as new biomarkers and drug delivery tools for the prevention and treatment of various diseases: current perspectives. Int J Mol Sci. 2021;22(15):7763.10.3390/ijms22157763Search in Google Scholar PubMed PubMed Central

Received: 2021-11-22
Revised: 2021-12-23
Accepted: 2022-01-03
Published Online: 2022-01-28

© 2022 Sameh A. Mohammed and Esraa Ibrahim A. Shaaban, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. Theoretical and experimental investigation of MWCNT dispersion effect on the elastic modulus of flexible PDMS/MWCNT nanocomposites
  3. Mechanical, morphological, and fracture-deformation behavior of MWCNTs-reinforced (Al–Cu–Mg–T351) alloy cast nanocomposites fabricated by optimized mechanical milling and powder metallurgy techniques
  4. Flammability and physical stability of sugar palm crystalline nanocellulose reinforced thermoplastic sugar palm starch/poly(lactic acid) blend bionanocomposites
  5. Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione
  6. Relationship between mechano-bactericidal activity and nanoblades density on chemically strengthened glass
  7. In situ regulation of microstructure and microwave-absorbing properties of FeSiAl through HNO3 oxidation
  8. Research on a mechanical model of magnetorheological fluid different diameter particles
  9. Nanomechanical and dynamic mechanical properties of rubber–wood–plastic composites
  10. Investigative properties of CeO2 doped with niobium: A combined characterization and DFT studies
  11. Miniaturized peptidomimetics and nano-vesiculation in endothelin types through probable nano-disk formation and structure property relationships of endothelins’ fragments
  12. N/S co-doped CoSe/C nanocubes as anode materials for Li-ion batteries
  13. Synergistic effects of halloysite nanotubes with metal and phosphorus additives on the optimal design of eco-friendly sandwich panels with maximum flame resistance and minimum weight
  14. Octreotide-conjugated silver nanoparticles for active targeting of somatostatin receptors and their application in a nebulized rat model
  15. Controllable morphology of Bi2S3 nanostructures formed via hydrothermal vulcanization of Bi2O3 thin-film layer and their photoelectrocatalytic performances
  16. Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment
  17. Enhancement of the mechanical properties of HDPE mineral nanocomposites by filler particles modulation of the matrix plastic/elastic behavior
  18. Effect of plasticizers on the properties of sugar palm nanocellulose/cinnamon essential oil reinforced starch bionanocomposite films
  19. Optimization of nano coating to reduce the thermal deformation of ball screws
  20. Preparation of efficient piezoelectric PVDF–HFP/Ni composite films by high electric field poling
  21. MHD dissipative Casson nanofluid liquid film flow due to an unsteady stretching sheet with radiation influence and slip velocity phenomenon
  22. Effects of nano-SiO2 modification on rubberised mortar and concrete with recycled coarse aggregates
  23. Mechanical and microscopic properties of fiber-reinforced coal gangue-based geopolymer concrete
  24. Effect of morphology and size on the thermodynamic stability of cerium oxide nanoparticles: Experiment and molecular dynamics calculation
  25. Mechanical performance of a CFRP composite reinforced via gelatin-CNTs: A study on fiber interfacial enhancement and matrix enhancement
  26. A practical review over surface modification, nanopatterns, emerging materials, drug delivery systems, and their biophysiochemical properties for dental implants: Recent progresses and advances
  27. HTR: An ultra-high speed algorithm for cage recognition of clathrate hydrates
  28. Effects of microalloying elements added by in situ synthesis on the microstructure of WCu composites
  29. A highly sensitive nanobiosensor based on aptamer-conjugated graphene-decorated rhodium nanoparticles for detection of HER2-positive circulating tumor cells
  30. Progressive collapse performance of shear strengthened RC frames by nano CFRP
  31. Core–shell heterostructured composites of carbon nanotubes and imine-linked hyperbranched polymers as metal-free Li-ion anodes
  32. A Galerkin strategy for tri-hybridized mixture in ethylene glycol comprising variable diffusion and thermal conductivity using non-Fourier’s theory
  33. Simple models for tensile modulus of shape memory polymer nanocomposites at ambient temperature
  34. Preparation and morphological studies of tin sulfide nanoparticles and use as efficient photocatalysts for the degradation of rhodamine B and phenol
  35. Polyethyleneimine-impregnated activated carbon nanofiber composited graphene-derived rice husk char for efficient post-combustion CO2 capture
  36. Electrospun nanofibers of Co3O4 nanocrystals encapsulated in cyclized-polyacrylonitrile for lithium storage
  37. Pitting corrosion induced on high-strength high carbon steel wire in high alkaline deaerated chloride electrolyte
  38. Formulation of polymeric nanoparticles loaded sorafenib; evaluation of cytotoxicity, molecular evaluation, and gene expression studies in lung and breast cancer cell lines
  39. Engineered nanocomposites in asphalt binders
  40. Influence of loading voltage, domain ratio, and additional load on the actuation of dielectric elastomer
  41. Thermally induced hex-graphene transitions in 2D carbon crystals
  42. The surface modification effect on the interfacial properties of glass fiber-reinforced epoxy: A molecular dynamics study
  43. Molecular dynamics study of deformation mechanism of interfacial microzone of Cu/Al2Cu/Al composites under tension
  44. Nanocolloid simulators of luminescent solar concentrator photovoltaic windows
  45. Compressive strength and anti-chloride ion penetration assessment of geopolymer mortar merging PVA fiber and nano-SiO2 using RBF–BP composite neural network
  46. Effect of 3-mercapto-1-propane sulfonate sulfonic acid and polyvinylpyrrolidone on the growth of cobalt pillar by electrodeposition
  47. Dynamics of convective slippery constraints on hybrid radiative Sutterby nanofluid flow by Galerkin finite element simulation
  48. Preparation of vanadium by the magnesiothermic self-propagating reduction and process control
  49. Microstructure-dependent photoelectrocatalytic activity of heterogeneous ZnO–ZnS nanosheets
  50. Cytotoxic and pro-inflammatory effects of molybdenum and tungsten disulphide on human bronchial cells
  51. Improving recycled aggregate concrete by compression casting and nano-silica
  52. Chemically reactive Maxwell nanoliquid flow by a stretching surface in the frames of Newtonian heating, nonlinear convection and radiative flux: Nanopolymer flow processing simulation
  53. Nonlinear dynamic and crack behaviors of carbon nanotubes-reinforced composites with various geometries
  54. Biosynthesis of copper oxide nanoparticles and its therapeutic efficacy against colon cancer
  55. Synthesis and characterization of smart stimuli-responsive herbal drug-encapsulated nanoniosome particles for efficient treatment of breast cancer
  56. Homotopic simulation for heat transport phenomenon of the Burgers nanofluids flow over a stretching cylinder with thermal convective and zero mass flux conditions
  57. Incorporation of copper and strontium ions in TiO2 nanotubes via dopamine to enhance hemocompatibility and cytocompatibility
  58. Mechanical, thermal, and barrier properties of starch films incorporated with chitosan nanoparticles
  59. Mechanical properties and microstructure of nano-strengthened recycled aggregate concrete
  60. Glucose-responsive nanogels efficiently maintain the stability and activity of therapeutic enzymes
  61. Tunning matrix rheology and mechanical performance of ultra-high performance concrete using cellulose nanofibers
  62. Flexible MXene/copper/cellulose nanofiber heat spreader films with enhanced thermal conductivity
  63. Promoted charge separation and specific surface area via interlacing of N-doped titanium dioxide nanotubes on carbon nitride nanosheets for photocatalytic degradation of Rhodamine B
  64. Elucidating the role of silicon dioxide and titanium dioxide nanoparticles in mitigating the disease of the eggplant caused by Phomopsis vexans, Ralstonia solanacearum, and root-knot nematode Meloidogyne incognita
  65. An implication of magnetic dipole in Carreau Yasuda liquid influenced by engine oil using ternary hybrid nanomaterial
  66. Robust synthesis of a composite phase of copper vanadium oxide with enhanced performance for durable aqueous Zn-ion batteries
  67. Tunning self-assembled phases of bovine serum albumin via hydrothermal process to synthesize novel functional hydrogel for skin protection against UVB
  68. A comparative experimental study on damping properties of epoxy nanocomposite beams reinforced with carbon nanotubes and graphene nanoplatelets
  69. Lightweight and hydrophobic Ni/GO/PVA composite aerogels for ultrahigh performance electromagnetic interference shielding
  70. Research on the auxetic behavior and mechanical properties of periodically rotating graphene nanostructures
  71. Repairing performances of novel cement mortar modified with graphene oxide and polyacrylate polymer
  72. Closed-loop recycling and fabrication of hydrophilic CNT films with high performance
  73. Design of thin-film configuration of SnO2–Ag2O composites for NO2 gas-sensing applications
  74. Study on stress distribution of SiC/Al composites based on microstructure models with microns and nanoparticles
  75. PVDF green nanofibers as potential carriers for improving self-healing and mechanical properties of carbon fiber/epoxy prepregs
  76. Osteogenesis capability of three-dimensionally printed poly(lactic acid)-halloysite nanotube scaffolds containing strontium ranelate
  77. Silver nanoparticles induce mitochondria-dependent apoptosis and late non-canonical autophagy in HT-29 colon cancer cells
  78. Preparation and bonding mechanisms of polymer/metal hybrid composite by nano molding technology
  79. Damage self-sensing and strain monitoring of glass-reinforced epoxy composite impregnated with graphene nanoplatelet and multiwalled carbon nanotubes
  80. Thermal analysis characterisation of solar-powered ship using Oldroyd hybrid nanofluids in parabolic trough solar collector: An optimal thermal application
  81. Pyrene-functionalized halloysite nanotubes for simultaneously detecting and separating Hg(ii) in aqueous media: A comprehensive comparison on interparticle and intraparticle excimers
  82. Fabrication of self-assembly CNT flexible film and its piezoresistive sensing behaviors
  83. Thermal valuation and entropy inspection of second-grade nanoscale fluid flow over a stretching surface by applying Koo–Kleinstreuer–Li relation
  84. Mechanical properties and microstructure of nano-SiO2 and basalt-fiber-reinforced recycled aggregate concrete
  85. Characterization and tribology performance of polyaniline-coated nanodiamond lubricant additives
  86. Combined impact of Marangoni convection and thermophoretic particle deposition on chemically reactive transport of nanofluid flow over a stretching surface
  87. Spark plasma extrusion of binder free hydroxyapatite powder
  88. An investigation on thermo-mechanical performance of graphene-oxide-reinforced shape memory polymer
  89. Effect of nanoadditives on the novel leather fiber/recycled poly(ethylene-vinyl-acetate) polymer composites for multifunctional applications: Fabrication, characterizations, and multiobjective optimization using central composite design
  90. Design selection for a hemispherical dimple core sandwich panel using hybrid multi-criteria decision-making methods
  91. Improving tensile strength and impact toughness of plasticized poly(lactic acid) biocomposites by incorporating nanofibrillated cellulose
  92. Green synthesis of spinel copper ferrite (CuFe2O4) nanoparticles and their toxicity
  93. The effect of TaC and NbC hybrid and mono-nanoparticles on AA2024 nanocomposites: Microstructure, strengthening, and artificial aging
  94. Excited-state geometry relaxation of pyrene-modified cellulose nanocrystals under UV-light excitation for detecting Fe3+
  95. Effect of CNTs and MEA on the creep of face-slab concrete at an early age
  96. Effect of deformation conditions on compression phase transformation of AZ31
  97. Application of MXene as a new generation of highly conductive coating materials for electromembrane-surrounded solid-phase microextraction
  98. A comparative study of the elasto-plastic properties for ceramic nanocomposites filled by graphene or graphene oxide nanoplates
  99. Encapsulation strategies for improving the biological behavior of CdS@ZIF-8 nanocomposites
  100. Biosynthesis of ZnO NPs from pumpkin seeds’ extract and elucidation of its anticancer potential against breast cancer
  101. Preliminary trials of the gold nanoparticles conjugated chrysin: An assessment of anti-oxidant, anti-microbial, and in vitro cytotoxic activities of a nanoformulated flavonoid
  102. Effect of micron-scale pores increased by nano-SiO2 sol modification on the strength of cement mortar
  103. Fractional simulations for thermal flow of hybrid nanofluid with aluminum oxide and titanium oxide nanoparticles with water and blood base fluids
  104. The effect of graphene nano-powder on the viscosity of water: An experimental study and artificial neural network modeling
  105. Development of a novel heat- and shear-resistant nano-silica gelling agent
  106. Characterization, biocompatibility and in vivo of nominal MnO2-containing wollastonite glass-ceramic
  107. Entropy production simulation of second-grade magnetic nanomaterials flowing across an expanding surface with viscidness dissipative flux
  108. Enhancement in structural, morphological, and optical properties of copper oxide for optoelectronic device applications
  109. Aptamer-functionalized chitosan-coated gold nanoparticle complex as a suitable targeted drug carrier for improved breast cancer treatment
  110. Performance and overall evaluation of nano-alumina-modified asphalt mixture
  111. Analysis of pure nanofluid (GO/engine oil) and hybrid nanofluid (GO–Fe3O4/engine oil): Novel thermal and magnetic features
  112. Synthesis of Ag@AgCl modified anatase/rutile/brookite mixed phase TiO2 and their photocatalytic property
  113. Mechanisms and influential variables on the abrasion resistance hydraulic concrete
  114. Synergistic reinforcement mechanism of basalt fiber/cellulose nanocrystals/polypropylene composites
  115. Achieving excellent oxidation resistance and mechanical properties of TiB2–B4C/carbon aerogel composites by quick-gelation and mechanical mixing
  116. Microwave-assisted sol–gel template-free synthesis and characterization of silica nanoparticles obtained from South African coal fly ash
  117. Pulsed laser-assisted synthesis of nano nickel(ii) oxide-anchored graphitic carbon nitride: Characterizations and their potential antibacterial/anti-biofilm applications
  118. Effects of nano-ZrSi2 on thermal stability of phenolic resin and thermal reusability of quartz–phenolic composites
  119. Benzaldehyde derivatives on tin electroplating as corrosion resistance for fabricating copper circuit
  120. Mechanical and heat transfer properties of 4D-printed shape memory graphene oxide/epoxy acrylate composites
  121. Coupling the vanadium-induced amorphous/crystalline NiFe2O4 with phosphide heterojunction toward active oxygen evolution reaction catalysts
  122. Graphene-oxide-reinforced cement composites mechanical and microstructural characteristics at elevated temperatures
  123. Gray correlation analysis of factors influencing compressive strength and durability of nano-SiO2 and PVA fiber reinforced geopolymer mortar
  124. Preparation of layered gradient Cu–Cr–Ti alloy with excellent mechanical properties, thermal stability, and electrical conductivity
  125. Recovery of Cr from chrome-containing leather wastes to develop aluminum-based composite material along with Al2O3 ceramic particles: An ingenious approach
  126. Mechanisms of the improved stiffness of flexible polymers under impact loading
  127. Anticancer potential of gold nanoparticles (AuNPs) using a battery of in vitro tests
  128. Review Articles
  129. Proposed approaches for coronaviruses elimination from wastewater: Membrane techniques and nanotechnology solutions
  130. Application of Pickering emulsion in oil drilling and production
  131. The contribution of microfluidics to the fight against tuberculosis
  132. Graphene-based biosensors for disease theranostics: Development, applications, and recent advancements
  133. Synthesis and encapsulation of iron oxide nanorods for application in magnetic hyperthermia and photothermal therapy
  134. Contemporary nano-architectured drugs and leads for ανβ3 integrin-based chemotherapy: Rationale and retrospect
  135. State-of-the-art review of fabrication, application, and mechanical properties of functionally graded porous nanocomposite materials
  136. Insights on magnetic spinel ferrites for targeted drug delivery and hyperthermia applications
  137. A review on heterogeneous oxidation of acetaminophen based on micro and nanoparticles catalyzed by different activators
  138. Early diagnosis of lung cancer using magnetic nanoparticles-integrated systems
  139. Advances in ZnO: Manipulation of defects for enhancing their technological potentials
  140. Efficacious nanomedicine track toward combating COVID-19
  141. A review of the design, processes, and properties of Mg-based composites
  142. Green synthesis of nanoparticles for varied applications: Green renewable resources and energy-efficient synthetic routes
  143. Two-dimensional nanomaterial-based polymer composites: Fundamentals and applications
  144. Recent progress and challenges in plasmonic nanomaterials
  145. Apoptotic cell-derived micro/nanosized extracellular vesicles in tissue regeneration
  146. Electronic noses based on metal oxide nanowires: A review
  147. Framework materials for supercapacitors
  148. An overview on the reproductive toxicity of graphene derivatives: Highlighting the importance
  149. Antibacterial nanomaterials: Upcoming hope to overcome antibiotic resistance crisis
  150. Research progress of carbon materials in the field of three-dimensional printing polymer nanocomposites
  151. A review of atomic layer deposition modelling and simulation methodologies: Density functional theory and molecular dynamics
  152. Recent advances in the preparation of PVDF-based piezoelectric materials
  153. Recent developments in tensile properties of friction welding of carbon fiber-reinforced composite: A review
  154. Comprehensive review of the properties of fly ash-based geopolymer with additive of nano-SiO2
  155. Perspectives in biopolymer/graphene-based composite application: Advances, challenges, and recommendations
  156. Graphene-based nanocomposite using new modeling molecular dynamic simulations for proposed neutralizing mechanism and real-time sensing of COVID-19
  157. Nanotechnology application on bamboo materials: A review
  158. Recent developments and future perspectives of biorenewable nanocomposites for advanced applications
  159. Nanostructured lipid carrier system: A compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery
  160. 3D printing customized design of human bone tissue implant and its application
  161. Design, preparation, and functionalization of nanobiomaterials for enhanced efficacy in current and future biomedical applications
  162. A brief review of nanoparticles-doped PEDOT:PSS nanocomposite for OLED and OPV
  163. Nanotechnology interventions as a putative tool for the treatment of dental afflictions
  164. Recent advancements in metal–organic frameworks integrating quantum dots (QDs@MOF) and their potential applications
  165. A focused review of short electrospun nanofiber preparation techniques for composite reinforcement
  166. Microstructural characteristics and nano-modification of interfacial transition zone in concrete: A review
  167. Latest developments in the upconversion nanotechnology for the rapid detection of food safety: A review
  168. Strategic applications of nano-fertilizers for sustainable agriculture: Benefits and bottlenecks
  169. Molecular dynamics application of cocrystal energetic materials: A review
  170. Synthesis and application of nanometer hydroxyapatite in biomedicine
  171. Cutting-edge development in waste-recycled nanomaterials for energy storage and conversion applications
  172. Biological applications of ternary quantum dots: A review
  173. Nanotherapeutics for hydrogen sulfide-involved treatment: An emerging approach for cancer therapy
  174. Application of antibacterial nanoparticles in orthodontic materials
  175. Effect of natural-based biological hydrogels combined with growth factors on skin wound healing
  176. Nanozymes – A route to overcome microbial resistance: A viewpoint
  177. Recent developments and applications of smart nanoparticles in biomedicine
  178. Contemporary review on carbon nanotube (CNT) composites and their impact on multifarious applications
  179. Interfacial interactions and reinforcing mechanisms of cellulose and chitin nanomaterials and starch derivatives for cement and concrete strength and durability enhancement: A review
  180. Diamond-like carbon films for tribological modification of rubber
  181. Layered double hydroxides (LDHs) modified cement-based materials: A systematic review
  182. Recent research progress and advanced applications of silica/polymer nanocomposites
  183. Modeling of supramolecular biopolymers: Leading the in silico revolution of tissue engineering and nanomedicine
  184. Recent advances in perovskites-based optoelectronics
  185. Biogenic synthesis of palladium nanoparticles: New production methods and applications
  186. A comprehensive review of nanofluids with fractional derivatives: Modeling and application
  187. Electrospinning of marine polysaccharides: Processing and chemical aspects, challenges, and future prospects
  188. Electrohydrodynamic printing for demanding devices: A review of processing and applications
  189. Rapid Communications
  190. Structural material with designed thermal twist for a simple actuation
  191. Recent advances in photothermal materials for solar-driven crude oil adsorption
https://doi.org/10.1515/ntrev-2022-0036
Keywords for this article
COVID-19; nanomedical diagnostics; nano-based therapeutics and vaccines
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Theoretical and experimental investigation of MWCNT dispersion effect on the elastic modulus of flexible PDMS/MWCNT nanocomposites
  3. Mechanical, morphological, and fracture-deformation behavior of MWCNTs-reinforced (Al–Cu–Mg–T351) alloy cast nanocomposites fabricated by optimized mechanical milling and powder metallurgy techniques
  4. Flammability and physical stability of sugar palm crystalline nanocellulose reinforced thermoplastic sugar palm starch/poly(lactic acid) blend bionanocomposites
  5. Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione
  6. Relationship between mechano-bactericidal activity and nanoblades density on chemically strengthened glass
  7. In situ regulation of microstructure and microwave-absorbing properties of FeSiAl through HNO3 oxidation
  8. Research on a mechanical model of magnetorheological fluid different diameter particles
  9. Nanomechanical and dynamic mechanical properties of rubber–wood–plastic composites
  10. Investigative properties of CeO2 doped with niobium: A combined characterization and DFT studies
  11. Miniaturized peptidomimetics and nano-vesiculation in endothelin types through probable nano-disk formation and structure property relationships of endothelins’ fragments
  12. N/S co-doped CoSe/C nanocubes as anode materials for Li-ion batteries
  13. Synergistic effects of halloysite nanotubes with metal and phosphorus additives on the optimal design of eco-friendly sandwich panels with maximum flame resistance and minimum weight
  14. Octreotide-conjugated silver nanoparticles for active targeting of somatostatin receptors and their application in a nebulized rat model
  15. Controllable morphology of Bi2S3 nanostructures formed via hydrothermal vulcanization of Bi2O3 thin-film layer and their photoelectrocatalytic performances
  16. Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment
  17. Enhancement of the mechanical properties of HDPE mineral nanocomposites by filler particles modulation of the matrix plastic/elastic behavior
  18. Effect of plasticizers on the properties of sugar palm nanocellulose/cinnamon essential oil reinforced starch bionanocomposite films
  19. Optimization of nano coating to reduce the thermal deformation of ball screws
  20. Preparation of efficient piezoelectric PVDF–HFP/Ni composite films by high electric field poling
  21. MHD dissipative Casson nanofluid liquid film flow due to an unsteady stretching sheet with radiation influence and slip velocity phenomenon
  22. Effects of nano-SiO2 modification on rubberised mortar and concrete with recycled coarse aggregates
  23. Mechanical and microscopic properties of fiber-reinforced coal gangue-based geopolymer concrete
  24. Effect of morphology and size on the thermodynamic stability of cerium oxide nanoparticles: Experiment and molecular dynamics calculation
  25. Mechanical performance of a CFRP composite reinforced via gelatin-CNTs: A study on fiber interfacial enhancement and matrix enhancement
  26. A practical review over surface modification, nanopatterns, emerging materials, drug delivery systems, and their biophysiochemical properties for dental implants: Recent progresses and advances
  27. HTR: An ultra-high speed algorithm for cage recognition of clathrate hydrates
  28. Effects of microalloying elements added by in situ synthesis on the microstructure of WCu composites
  29. A highly sensitive nanobiosensor based on aptamer-conjugated graphene-decorated rhodium nanoparticles for detection of HER2-positive circulating tumor cells
  30. Progressive collapse performance of shear strengthened RC frames by nano CFRP
  31. Core–shell heterostructured composites of carbon nanotubes and imine-linked hyperbranched polymers as metal-free Li-ion anodes
  32. A Galerkin strategy for tri-hybridized mixture in ethylene glycol comprising variable diffusion and thermal conductivity using non-Fourier’s theory
  33. Simple models for tensile modulus of shape memory polymer nanocomposites at ambient temperature
  34. Preparation and morphological studies of tin sulfide nanoparticles and use as efficient photocatalysts for the degradation of rhodamine B and phenol
  35. Polyethyleneimine-impregnated activated carbon nanofiber composited graphene-derived rice husk char for efficient post-combustion CO2 capture
  36. Electrospun nanofibers of Co3O4 nanocrystals encapsulated in cyclized-polyacrylonitrile for lithium storage
  37. Pitting corrosion induced on high-strength high carbon steel wire in high alkaline deaerated chloride electrolyte
  38. Formulation of polymeric nanoparticles loaded sorafenib; evaluation of cytotoxicity, molecular evaluation, and gene expression studies in lung and breast cancer cell lines
  39. Engineered nanocomposites in asphalt binders
  40. Influence of loading voltage, domain ratio, and additional load on the actuation of dielectric elastomer
  41. Thermally induced hex-graphene transitions in 2D carbon crystals
  42. The surface modification effect on the interfacial properties of glass fiber-reinforced epoxy: A molecular dynamics study
  43. Molecular dynamics study of deformation mechanism of interfacial microzone of Cu/Al2Cu/Al composites under tension
  44. Nanocolloid simulators of luminescent solar concentrator photovoltaic windows
  45. Compressive strength and anti-chloride ion penetration assessment of geopolymer mortar merging PVA fiber and nano-SiO2 using RBF–BP composite neural network
  46. Effect of 3-mercapto-1-propane sulfonate sulfonic acid and polyvinylpyrrolidone on the growth of cobalt pillar by electrodeposition
  47. Dynamics of convective slippery constraints on hybrid radiative Sutterby nanofluid flow by Galerkin finite element simulation
  48. Preparation of vanadium by the magnesiothermic self-propagating reduction and process control
  49. Microstructure-dependent photoelectrocatalytic activity of heterogeneous ZnO–ZnS nanosheets
  50. Cytotoxic and pro-inflammatory effects of molybdenum and tungsten disulphide on human bronchial cells
  51. Improving recycled aggregate concrete by compression casting and nano-silica
  52. Chemically reactive Maxwell nanoliquid flow by a stretching surface in the frames of Newtonian heating, nonlinear convection and radiative flux: Nanopolymer flow processing simulation
  53. Nonlinear dynamic and crack behaviors of carbon nanotubes-reinforced composites with various geometries
  54. Biosynthesis of copper oxide nanoparticles and its therapeutic efficacy against colon cancer
  55. Synthesis and characterization of smart stimuli-responsive herbal drug-encapsulated nanoniosome particles for efficient treatment of breast cancer
  56. Homotopic simulation for heat transport phenomenon of the Burgers nanofluids flow over a stretching cylinder with thermal convective and zero mass flux conditions
  57. Incorporation of copper and strontium ions in TiO2 nanotubes via dopamine to enhance hemocompatibility and cytocompatibility
  58. Mechanical, thermal, and barrier properties of starch films incorporated with chitosan nanoparticles
  59. Mechanical properties and microstructure of nano-strengthened recycled aggregate concrete
  60. Glucose-responsive nanogels efficiently maintain the stability and activity of therapeutic enzymes
  61. Tunning matrix rheology and mechanical performance of ultra-high performance concrete using cellulose nanofibers
  62. Flexible MXene/copper/cellulose nanofiber heat spreader films with enhanced thermal conductivity
  63. Promoted charge separation and specific surface area via interlacing of N-doped titanium dioxide nanotubes on carbon nitride nanosheets for photocatalytic degradation of Rhodamine B
  64. Elucidating the role of silicon dioxide and titanium dioxide nanoparticles in mitigating the disease of the eggplant caused by Phomopsis vexans, Ralstonia solanacearum, and root-knot nematode Meloidogyne incognita
  65. An implication of magnetic dipole in Carreau Yasuda liquid influenced by engine oil using ternary hybrid nanomaterial
  66. Robust synthesis of a composite phase of copper vanadium oxide with enhanced performance for durable aqueous Zn-ion batteries
  67. Tunning self-assembled phases of bovine serum albumin via hydrothermal process to synthesize novel functional hydrogel for skin protection against UVB
  68. A comparative experimental study on damping properties of epoxy nanocomposite beams reinforced with carbon nanotubes and graphene nanoplatelets
  69. Lightweight and hydrophobic Ni/GO/PVA composite aerogels for ultrahigh performance electromagnetic interference shielding
  70. Research on the auxetic behavior and mechanical properties of periodically rotating graphene nanostructures
  71. Repairing performances of novel cement mortar modified with graphene oxide and polyacrylate polymer
  72. Closed-loop recycling and fabrication of hydrophilic CNT films with high performance
  73. Design of thin-film configuration of SnO2–Ag2O composites for NO2 gas-sensing applications
  74. Study on stress distribution of SiC/Al composites based on microstructure models with microns and nanoparticles
  75. PVDF green nanofibers as potential carriers for improving self-healing and mechanical properties of carbon fiber/epoxy prepregs
  76. Osteogenesis capability of three-dimensionally printed poly(lactic acid)-halloysite nanotube scaffolds containing strontium ranelate
  77. Silver nanoparticles induce mitochondria-dependent apoptosis and late non-canonical autophagy in HT-29 colon cancer cells
  78. Preparation and bonding mechanisms of polymer/metal hybrid composite by nano molding technology
  79. Damage self-sensing and strain monitoring of glass-reinforced epoxy composite impregnated with graphene nanoplatelet and multiwalled carbon nanotubes
  80. Thermal analysis characterisation of solar-powered ship using Oldroyd hybrid nanofluids in parabolic trough solar collector: An optimal thermal application
  81. Pyrene-functionalized halloysite nanotubes for simultaneously detecting and separating Hg(ii) in aqueous media: A comprehensive comparison on interparticle and intraparticle excimers
  82. Fabrication of self-assembly CNT flexible film and its piezoresistive sensing behaviors
  83. Thermal valuation and entropy inspection of second-grade nanoscale fluid flow over a stretching surface by applying Koo–Kleinstreuer–Li relation
  84. Mechanical properties and microstructure of nano-SiO2 and basalt-fiber-reinforced recycled aggregate concrete
  85. Characterization and tribology performance of polyaniline-coated nanodiamond lubricant additives
  86. Combined impact of Marangoni convection and thermophoretic particle deposition on chemically reactive transport of nanofluid flow over a stretching surface
  87. Spark plasma extrusion of binder free hydroxyapatite powder
  88. An investigation on thermo-mechanical performance of graphene-oxide-reinforced shape memory polymer
  89. Effect of nanoadditives on the novel leather fiber/recycled poly(ethylene-vinyl-acetate) polymer composites for multifunctional applications: Fabrication, characterizations, and multiobjective optimization using central composite design
  90. Design selection for a hemispherical dimple core sandwich panel using hybrid multi-criteria decision-making methods
  91. Improving tensile strength and impact toughness of plasticized poly(lactic acid) biocomposites by incorporating nanofibrillated cellulose
  92. Green synthesis of spinel copper ferrite (CuFe2O4) nanoparticles and their toxicity
  93. The effect of TaC and NbC hybrid and mono-nanoparticles on AA2024 nanocomposites: Microstructure, strengthening, and artificial aging
  94. Excited-state geometry relaxation of pyrene-modified cellulose nanocrystals under UV-light excitation for detecting Fe3+
  95. Effect of CNTs and MEA on the creep of face-slab concrete at an early age
  96. Effect of deformation conditions on compression phase transformation of AZ31
  97. Application of MXene as a new generation of highly conductive coating materials for electromembrane-surrounded solid-phase microextraction
  98. A comparative study of the elasto-plastic properties for ceramic nanocomposites filled by graphene or graphene oxide nanoplates
  99. Encapsulation strategies for improving the biological behavior of CdS@ZIF-8 nanocomposites
  100. Biosynthesis of ZnO NPs from pumpkin seeds’ extract and elucidation of its anticancer potential against breast cancer
  101. Preliminary trials of the gold nanoparticles conjugated chrysin: An assessment of anti-oxidant, anti-microbial, and in vitro cytotoxic activities of a nanoformulated flavonoid
  102. Effect of micron-scale pores increased by nano-SiO2 sol modification on the strength of cement mortar
  103. Fractional simulations for thermal flow of hybrid nanofluid with aluminum oxide and titanium oxide nanoparticles with water and blood base fluids
  104. The effect of graphene nano-powder on the viscosity of water: An experimental study and artificial neural network modeling
  105. Development of a novel heat- and shear-resistant nano-silica gelling agent
  106. Characterization, biocompatibility and in vivo of nominal MnO2-containing wollastonite glass-ceramic
  107. Entropy production simulation of second-grade magnetic nanomaterials flowing across an expanding surface with viscidness dissipative flux
  108. Enhancement in structural, morphological, and optical properties of copper oxide for optoelectronic device applications
  109. Aptamer-functionalized chitosan-coated gold nanoparticle complex as a suitable targeted drug carrier for improved breast cancer treatment
  110. Performance and overall evaluation of nano-alumina-modified asphalt mixture
  111. Analysis of pure nanofluid (GO/engine oil) and hybrid nanofluid (GO–Fe3O4/engine oil): Novel thermal and magnetic features
  112. Synthesis of Ag@AgCl modified anatase/rutile/brookite mixed phase TiO2 and their photocatalytic property
  113. Mechanisms and influential variables on the abrasion resistance hydraulic concrete
  114. Synergistic reinforcement mechanism of basalt fiber/cellulose nanocrystals/polypropylene composites
  115. Achieving excellent oxidation resistance and mechanical properties of TiB2–B4C/carbon aerogel composites by quick-gelation and mechanical mixing
  116. Microwave-assisted sol–gel template-free synthesis and characterization of silica nanoparticles obtained from South African coal fly ash
  117. Pulsed laser-assisted synthesis of nano nickel(ii) oxide-anchored graphitic carbon nitride: Characterizations and their potential antibacterial/anti-biofilm applications
  118. Effects of nano-ZrSi2 on thermal stability of phenolic resin and thermal reusability of quartz–phenolic composites
  119. Benzaldehyde derivatives on tin electroplating as corrosion resistance for fabricating copper circuit
  120. Mechanical and heat transfer properties of 4D-printed shape memory graphene oxide/epoxy acrylate composites
  121. Coupling the vanadium-induced amorphous/crystalline NiFe2O4 with phosphide heterojunction toward active oxygen evolution reaction catalysts
  122. Graphene-oxide-reinforced cement composites mechanical and microstructural characteristics at elevated temperatures
  123. Gray correlation analysis of factors influencing compressive strength and durability of nano-SiO2 and PVA fiber reinforced geopolymer mortar
  124. Preparation of layered gradient Cu–Cr–Ti alloy with excellent mechanical properties, thermal stability, and electrical conductivity
  125. Recovery of Cr from chrome-containing leather wastes to develop aluminum-based composite material along with Al2O3 ceramic particles: An ingenious approach
  126. Mechanisms of the improved stiffness of flexible polymers under impact loading
  127. Anticancer potential of gold nanoparticles (AuNPs) using a battery of in vitro tests
  128. Review Articles
  129. Proposed approaches for coronaviruses elimination from wastewater: Membrane techniques and nanotechnology solutions
  130. Application of Pickering emulsion in oil drilling and production
  131. The contribution of microfluidics to the fight against tuberculosis
  132. Graphene-based biosensors for disease theranostics: Development, applications, and recent advancements
  133. Synthesis and encapsulation of iron oxide nanorods for application in magnetic hyperthermia and photothermal therapy
  134. Contemporary nano-architectured drugs and leads for ανβ3 integrin-based chemotherapy: Rationale and retrospect
  135. State-of-the-art review of fabrication, application, and mechanical properties of functionally graded porous nanocomposite materials
  136. Insights on magnetic spinel ferrites for targeted drug delivery and hyperthermia applications
  137. A review on heterogeneous oxidation of acetaminophen based on micro and nanoparticles catalyzed by different activators
  138. Early diagnosis of lung cancer using magnetic nanoparticles-integrated systems
  139. Advances in ZnO: Manipulation of defects for enhancing their technological potentials
  140. Efficacious nanomedicine track toward combating COVID-19
  141. A review of the design, processes, and properties of Mg-based composites
  142. Green synthesis of nanoparticles for varied applications: Green renewable resources and energy-efficient synthetic routes
  143. Two-dimensional nanomaterial-based polymer composites: Fundamentals and applications
  144. Recent progress and challenges in plasmonic nanomaterials
  145. Apoptotic cell-derived micro/nanosized extracellular vesicles in tissue regeneration
  146. Electronic noses based on metal oxide nanowires: A review
  147. Framework materials for supercapacitors
  148. An overview on the reproductive toxicity of graphene derivatives: Highlighting the importance
  149. Antibacterial nanomaterials: Upcoming hope to overcome antibiotic resistance crisis
  150. Research progress of carbon materials in the field of three-dimensional printing polymer nanocomposites
  151. A review of atomic layer deposition modelling and simulation methodologies: Density functional theory and molecular dynamics
  152. Recent advances in the preparation of PVDF-based piezoelectric materials
  153. Recent developments in tensile properties of friction welding of carbon fiber-reinforced composite: A review
  154. Comprehensive review of the properties of fly ash-based geopolymer with additive of nano-SiO2
  155. Perspectives in biopolymer/graphene-based composite application: Advances, challenges, and recommendations
  156. Graphene-based nanocomposite using new modeling molecular dynamic simulations for proposed neutralizing mechanism and real-time sensing of COVID-19
  157. Nanotechnology application on bamboo materials: A review
  158. Recent developments and future perspectives of biorenewable nanocomposites for advanced applications
  159. Nanostructured lipid carrier system: A compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery
  160. 3D printing customized design of human bone tissue implant and its application
  161. Design, preparation, and functionalization of nanobiomaterials for enhanced efficacy in current and future biomedical applications
  162. A brief review of nanoparticles-doped PEDOT:PSS nanocomposite for OLED and OPV
  163. Nanotechnology interventions as a putative tool for the treatment of dental afflictions
  164. Recent advancements in metal–organic frameworks integrating quantum dots (QDs@MOF) and their potential applications
  165. A focused review of short electrospun nanofiber preparation techniques for composite reinforcement
  166. Microstructural characteristics and nano-modification of interfacial transition zone in concrete: A review
  167. Latest developments in the upconversion nanotechnology for the rapid detection of food safety: A review
  168. Strategic applications of nano-fertilizers for sustainable agriculture: Benefits and bottlenecks
  169. Molecular dynamics application of cocrystal energetic materials: A review
  170. Synthesis and application of nanometer hydroxyapatite in biomedicine
  171. Cutting-edge development in waste-recycled nanomaterials for energy storage and conversion applications
  172. Biological applications of ternary quantum dots: A review
  173. Nanotherapeutics for hydrogen sulfide-involved treatment: An emerging approach for cancer therapy
  174. Application of antibacterial nanoparticles in orthodontic materials
  175. Effect of natural-based biological hydrogels combined with growth factors on skin wound healing
  176. Nanozymes – A route to overcome microbial resistance: A viewpoint
  177. Recent developments and applications of smart nanoparticles in biomedicine
  178. Contemporary review on carbon nanotube (CNT) composites and their impact on multifarious applications
  179. Interfacial interactions and reinforcing mechanisms of cellulose and chitin nanomaterials and starch derivatives for cement and concrete strength and durability enhancement: A review
  180. Diamond-like carbon films for tribological modification of rubber
  181. Layered double hydroxides (LDHs) modified cement-based materials: A systematic review
  182. Recent research progress and advanced applications of silica/polymer nanocomposites
  183. Modeling of supramolecular biopolymers: Leading the in silico revolution of tissue engineering and nanomedicine
  184. Recent advances in perovskites-based optoelectronics
  185. Biogenic synthesis of palladium nanoparticles: New production methods and applications
  186. A comprehensive review of nanofluids with fractional derivatives: Modeling and application
  187. Electrospinning of marine polysaccharides: Processing and chemical aspects, challenges, and future prospects
  188. Electrohydrodynamic printing for demanding devices: A review of processing and applications
  189. Rapid Communications
  190. Structural material with designed thermal twist for a simple actuation
  191. Recent advances in photothermal materials for solar-driven crude oil adsorption
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 9.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/ntrev-2022-0036/html
Scroll to top button