Cutting-edge: bionanomaterial solutions in the battle against Severe Acute Respiratory Syndrome Coronavirus 2

Vanguarda: soluções de bionanomateriais na batalha contra a Síndrome Respiratória Aguda Grave Coronavírus 2

Abstract

Amidst the ongoing COVID-19 pandemic, the imperative of our time resides in crafting stratagems of utmost precision to confront the relentless SARS-CoV-2 and quell its inexorable proliferation. A paradigm-shifting weapon in this battle lies in the realm of nanoparticles, where the amalgamation of cutting-edge nanochemistry begets a cornucopia of inventive techniques and methodologies designed to thwart the advances of this pernicious pathogen. Nanochemistry, an artful fusion of chemistry and nanoscience, provides a fertile landscape for researchers to craft innovative shields against infection. Within this intricate tapestry, nanoparticles emerge as champions, offering multifaceted solutions encompassing detection, treatment, prevention, and the precise targeting of SARS-CoV-2 incursions. Noteworthy among these innovations, the Silver (Ag) Respi-strips command our attention. These strips stand as exemplars of ingenuity, illuminating the path to swift and precise test detection. Moreover, the integration of Ag-based textile materials into the arsenal against viral propagation opens a promising avenue to curtail the virus's insidious reach. The indomitable force of iron nanoparticles, duly sanctioned by the esteemed FDA, shines as a beacon of hope in the treatment of infection. Their interaction with the glycoprotein spikes of the virus unleashes an inhibitory action of profound consequence. Meanwhile, the domain of diagnostics has been revolutionized by the advent of Magnetic Nanoparticles (MNPs). Their role in automating nucleic acid extraction and purification has proven indispensable, particularly in the diagnostic milieu of SARS-CoV-2. These MNPs wield a magnetic allure, streamlining diagnostic processes with unmatched precision. In this realm of nano-wonders, Gold nanoparticles rise as formidable sentinels, poised at the intersection of versatility and innovation. Their functionalization via a kaleidoscope of functional groups or in concert with antiviral drug combinations augments their prowess. These microscopic champions effectively hinder viral ingress into host cells and orchestrate the controlled release of antiviral agents, casting a profound influence on the course of viral infections. The pandemic landscape has borne witness to the ascendancy of nanotechnology, unveiling an arsenal of nanoparticle-based strategies that promise to defy, detect, treat, and ultimately vanquish SARS-CoV-2. The future beckons, and within the infinitesimal realm of nanoparticles, we find the promise of a brighter, healthier tomorrow.

Keywords:
SARS-CoV-2; COVID-19; magnetic nanoparticles; iron nanoparticles; silver nanoparticles; gold nanoparticles

Resumo

No meio da pandemia de COVID-19, em curso, o imperativo do nosso tempo reside na elaboração de estratagemas de máxima precisão para enfrentar o implacável SARS-CoV-2 e reprimir a sua proliferação inexorável. Uma arma de mudança de paradigma nesta batalha reside no domínio das nanopartículas, em que a fusão de nanoquímica de ponta gera uma cornucópia de técnicas e metodologias inventivas concebidas para impedir os avanços deste patógeno pernicioso. A nanoquímica, uma fusão engenhosa de química e nanociência, proporciona um cenário fértil para os investigadores criarem escudos inovadores contra infecções. Dentro desta intrincada tapeçaria, as nanopartículas emergem como campeãs, oferecendo soluções multifacetadas que abrangem detecção, tratamento, prevenção e direcionamento preciso de incursões de SARS-CoV-2. Destacam-se entre essas inovações as tiras Silver (Ag) Respi, que chamam nossa atenção. Essas tiras são exemplos de engenhosidade, iluminando o caminho para uma detecção rápida e precisa no teste de SARS-CoV-2. Além disso, a integração de materiais têxteis baseados em Ag no arsenal contra a propagação viral abre um caminho promissor para reduzir o alcance insidioso do vírus. A força indomável das nanopartículas de ferro, devidamente sancionadas pela estimada FDA, brilha como um farol de esperança no tratamento de infecções. A sua interação com os picos de glicoproteínas do vírus desencadeia uma ação inibitória de profundas consequências. Enquanto isso, o domínio do diagnóstico foi revolucionado pelo advento das Nanopartículas Magnéticas (MNPs). O seu papel na automatização da extração e purificação de ácidos nucleicos revelou-se indispensável, particularmente no meio diagnóstico do SARS-CoV-2. Essas MNPs exercem um fascínio magnético, agilizando processos de diagnóstico com precisão incomparável. Neste reino de nanomaravilhas, as nanopartículas de ouro surgem como sentinelas formidáveis, posicionadas na intersecção entre versatilidade e inovação. A sua funcionalização através de um caleidoscópio de grupos funcionais ou em conjunto com combinações de medicamentos antivirais aumenta a sua capacidade. Esses campeões microscópicos impedem efetivamente a entrada viral nas células hospedeiras e orquestram a liberação controlada de agentes antivirais, exercendo uma influência profunda no curso das infecções virais. O cenário pandêmico testemunhou a ascendência da nanotecnologia, revelando um arsenal de estratégias baseadas em nanopartículas que prometem desafiar, detectar, tratar e, em última análise, vencer o SARS-CoV-2. O futuro acena e, no reino infinitesimal das nanopartículas, encontramos a promessa de um amanhã mais brilhante e saudável.

Palavras-chave:
SARS-CoV-2; COVID-19; nanopartículas magnéticas; nanopartículas de ferro; nanopartículas de prata; nanopartículas de ouro

1. Introduction

In December 2019, a momentous event transpired in Wuhan, China, with the emergence of the inital case of Severe Acute Respiratory Syndrome, precipitated by the advent of Coronavirus 2 (SARS-CoV-2). This event swiftly unfolded into a global pandemic of unparalleled magnitude, a phenomenon acknowledged with promptitude by the World Health Organization in 2020 (WHO, 2020). SARS-CoV-2, a formidable pathogen, deploys a multifaceted transmission strategy, capitalizing on close interpersonal contact, the exchange of minuscule respiratory droplets between individuals, and surface or fomite contamination as vectors of propagation. In response to this existential crisis, a comprehensive array of interventions has been enacted on a global scale. These encompass obligatory mask mandates, the rigorous enforcement of meticulous hand hygiene protocols, the stringent adherence to physical distancing measures, voluntary self-isolation measures, the meticulous disinfection of communal surfaces, the imposition of rigorous lockdowns, and the consequential closure of educational institutions and workplaces, all meticulously orchestrated to curb the relentless spread of the virus (WHO, 2020).

At the heart of SARS-CoV-2 diagnostics, the gold standard remains the real-time reverse transcriptase polymerase chain reaction (RT-PCR), an esteemed method celebrated for its unwavering precision and reliability (Chu et al., 2020; Saeed et al., 2021a). Within the intricate tapestry of the virus's genetic makeup lies its genomic architecture, a positive-sense single-stranded RNA genome, spanning an expansive spectrum from 26 to 32 kilobases (Li et al., 2020). This viral entity presents a complex structural composition, featuring indispensable proteins such as the Envelope (E) protein, the Spike (S) glycoprotein, the Hemagglutinin-esterase (HE) protein, the Nucleocapsid (N) protein, and the Membrane (M) protein. Particularly noteworthy is the Spike (S) glycoprotein, comprising two pivotal subunits, S1 and S2. The S1 subunit is the harbinger of a receptor binding domain (RBD), orchestrating interactions with the host angiotensin-converting enzyme II (ACE2) receptor, culminating in the fusion of the virus with the host cell. Complementing this intricate process, the S2 subunit plays an indispensable role in facilitating viral entry (Huang et al., 2020; Tai et al., 2020).

In the realm of scientific exploration, the interdisciplinary field of Nanoscience has emerged as a beacon of enlightenment, illuminating the intrinsic properties of nano-sized particles, championed by luminaries such as Sergeev and his contemporaries. Within this captivating realm, nanoparticles, atom clusters inhabiting the nanometer scale, specifically ranging from 1-100 nm, have emerged as a focal point, nurturing the burgeoning field of Nano-Chemistry, a trajectory championed by visionaries like Sergeev and Shabatina (Abou El-Nour et al., 2010; Akbarzadeh et al., 2012; Amara et al., 2009).

The primary aim of this study is to harness the potential of nanoparticles as cutting-edge tools in the battle against SARS-CoV-2 during the ongoing COVID-19 pandemic. With a multifaceted approach, the research seeks to achieve several key objectives. First, it aims to explore the application of various nanoparticles, such as silver (Ag), iron, magnetic nanoparticles (MNPs), and gold nanoparticles, in the accurate and rapid detection of the SARS-CoV-2 virus. Additionally, the study strives to evaluate the effectiveness of iron nanoparticles, which have gained FDA approval, as a means of treating SARS-CoV-2 infections by targeting the virus's glycoprotein spikes. Furthermore, it aspires to investigate the utilization of Ag-based textile materials to impede the viral spread, thereby contributing to the prevention of COVID-19 transmission. Finally, the research aims to harness the capabilities of MNPs in automated nucleic acid extraction and purification, with a specific emphasis on their role in diagnosing SARS-CoV-2 infections. Overall, this study endeavors to leverage the remarkable properties of nanoparticles and the advances in nanochemistry to develop innovative techniques and strategies that address multiple facets of the SARS-CoV-2 virus, including diagnosis, treatment, prevention, and targeted intervention. Globally viral infections are mounting over a period of time (Saeed et al., 2023a, b, c, 2024; Saeed and Piracha, 2023; Piracha and Saeed, 2023, Piracha et al., 2023, 2024; Uppal et al., 2024). Adequate precautionary measures should be taken for the prevention of viral diseases (Saeed et al., 2021a, b, c).

2. Leveraging Nano-medicines in the Battle Against COVID-19

In the context of the ongoing COVID-19 pandemic, the role of nano-medicines stands as an innovative and promising frontier in the fight against viral infections. Photodynamic therapy (PDT), a well-established therapeutic approach, has garnered attention for its remarkable effectiveness in inactivating mammalian viruses (Costa et al., 2012). Notably, enveloped viruses, distinguished by their lipid-based membranes, exhibit a heightened responsiveness to photodynamic therapy (PDT) compared to their non-enveloped counterparts. Further enhancing the therapeutic landscape, nanotechnology has emerged as a formidable ally in augmenting the efficacy of antiviral photodynamic therapy (aPDT) (Banfield and Zhang, 2001; Beveridge et al., 2011). Nanotechnology's intricate interplay with aPDT has unlocked new avenues for combating viral infections.

Moreover, nano-medicines have unveiled an array of pioneering methodologies, capitalizing on the utilization of tailored nanoparticles (NPs) as photosensitizers, thereby enabling the precise photo-inactivation of pathogens through the photodynamic effect. A remarkable stride in this domain involves the strategic deployment of multivalent nanomedicines, engineered with precision to target the binding interfaces between pathogens and host cells. This strategic approach effectively halts viral entry into the host (Campos et al., 2020).

Within the intricate clinical terrain of COVID-19, the occurrence of life-threatening blood clotting events leading to strokes and sudden fatalities among afflicted patients has raised significant concerns. Recent research has underscored the paramount importance of early diagnosis, facilitated by d-dimer biomarkers among COVID-19 patients. This early diagnostic tool not only aids in timely therapeutic decision-making but also offers critical insights into treatment options (Saeed et al., 2022). Furthermore, the prevention of these thrombotic events can be further advanced through the synergistic collaboration between nano-medicines and proteomic methodologies (Saeed et al., 2021a).

Nano-medicines have assumed an indispensable role in the ongoing confrontation with the COVID-19 pandemic, proffering an array of innovative solutions that transcend the conventional boundaries of medical science. These diminutive yet highly engineered materials, typically operating at the nanometer scale, have exhibited extraordinary versatility and efficacy across several pivotal facets of pandemic management (Mulfinger et al., 2007). Foremost among their contributions is the capacity to revolutionize drug delivery. Nano-sized drug carriers, encompassing entities like liposomes and nanoparticles, hold the ability to encapsulate antiviral agents, monoclonal antibodies, or RNA-based vaccines with exquisite precision. In so doing, these nano-encapsulations not only shield the therapeutic payloads from premature degradation but also orchestrate a controlled and sustained release, thereby amplifying drug efficacy while minimizing undesirable side effects. This targeted drug delivery assumes profound significance when addressing viral infections, especially in the context of respiratory pathogens like SARS-CoV-2.

Within the sphere of vaccine development, nano-formulations have risen to prominence. Notable examples include lipid nanoparticles that serve as veritable chaperones for messenger RNA (mRNA) vaccines, exemplified by the Pfizer-BioNTech and Moderna vaccines. This intricate alliance stabilizes the fragile mRNA constructs and facilitates their cellular uptake, ultimately yielding robust and enduring immune responses. Nano-medicines, by expediting vaccine development, have propelled the rapid deployment of potent immunization strategies against COVID-19.

Extending their influence beyond vaccines and drug delivery, nano-medicines exert a pivotal role in diagnostic and therapeutic paradigms. Nanostructured materials underpin the development of highly sensitive diagnostic modalities, encompassing point-of-care assays and biosensors that hold the potential to revolutionize screening and surveillance efforts. Furthermore, these nanomaterials can be meticulously tailored to transport imaging agents, thereby affording the precise real-time tracking of viral infections within the body.

In the therapeutic arena, nano-medicines emerge as avant-garde solutions for countering COVID-19-related complications. They can be meticulously engineered to address specific facets of the disease, including the hyperinflammatory response characteristic of severe cases. Nano-based therapies are designed to modulate the immune system, deliver potent anti-inflammatory agents, or neutralize the deleterious pro-inflammatory cytokines, offering a potential avenue for averting the cataclysmic cytokine storm associated with severe COVID-19.

Moreover, nano-medicines have been instrumental in the evolution of antiviral photodynamic therapy (aPDT). This groundbreaking approach harnesses nanoparticles as adept photosensitizers to orchestrate the photo-inactivation of the virus, a manifestation of the photodynamic effect. By directing their action towards the viral envelope, aPDT can efficaciously neutralize enveloped viruses such as SARS-CoV-2, thereby representing a tantalizing prospect in the realm of antiviral therapeutics.

This comprehensive review embarks on a profound exploration of the evolving role of nano-medicines in the context of combating COVID-19. It delves into their pivotal contributions in the domains of photodynamic therapy, targeted pathogen inactivation, and thrombotic event prevention. These groundbreaking advancements underscore the transformative potential of nano-medicines in the ongoing battle against this global health crisis.

3. Nanoparticles’ Crucial Role in Combating COVID-19

Nanoparticles possess the remarkable ability to intricately modulate physical, biological, and chemical attributes, courtesy of their exceptional surface-to-volume ratios (Cesewski and Johnson, 2020). Among these nanoparticles, silver, abundant and historically renowned for its enduring stability, stands as a formidable contender. Silver nanoparticles, distinguished by their capacity to yield consistent monodisperse products at scale without necessitating size-based sorting, manifest superior levels of purity, stability, and yield when compared to their counterparts. The underpinning tenets of first-principle electronic structure theory serve as the bedrock for comprehending their chemical stability, structural nuances, and their electronic and optical properties (Desireddy et al., 2013).

Nanoparticles have assumed a pivotal role in the global battle against COVID-19 due to their unique properties and versatile applications. Nanoparticles excel in the domain of drug delivery. These minuscule carriers can encapsulate antiviral medications, vaccines, and other therapeutic agents, shielding them from premature degradation. Additionally, they allow for controlled and sustained release, amplifying the efficacy of these drugs while minimizing side effects. Especially relevant to COVID-19, nanoparticles can be engineered to target the respiratory system, the primary site of infection, ensuring that drugs are delivered precisely where they are needed. Nanoparticles have played a pivotal role in the development of COVID-19 vaccines. For instance, lipid nanoparticles serve as protective vehicles for messenger RNA (mRNA) vaccines, such as those developed by Pfizer-BioNTech and Moderna. This role is crucial in stabilizing the delicate mRNA molecules and facilitating their cellular uptake, resulting in robust and enduring immune responses. Beyond drug delivery and vaccines, nanoparticles have demonstrated their utility in diagnostic tools. Nanoparticles can be engineered to bind to specific viral proteins, making them integral components of highly sensitive diagnostic assays, including rapid tests and biosensors. They hold the potential to revolutionize COVID-19 testing, enabling rapid and accurate detection of the virus. Furthermore, nanoparticles contribute to the development of therapeutic approaches. In the context of COVID-19, they are used to target specific aspects of the disease, such as the hyperinflammatory response observed in severe cases. Nanoparticle-based therapies can modulate the immune system, deliver anti-inflammatory agents, or neutralize pro-inflammatory cytokines, potentially preventing the severe cytokine storm that characterizes severe COVID-19 cases.

4. Silver Nanoparticles (AgNPs)

These silver nanoparticles exhibit a vibrant, intense yellow hue, a stark contrast to their ionic and bulk silver counterparts. In the pursuit of illuminating their size, students undertake the synthesis of colloidal silver, employing the precision of visible spectroscopy. To embark on this scientific journey, they rely on dilute solutions, a Spectronic-20 spectrophotometer, and the aid of a magnetic stir plate. The synthetic route chosen is the borohydride synthesis, yielding particles spanning the range of 400nm. To glean insights into their dimensions, transmission electron microscopy (TEM) images are harnessed.

Two distinct approaches unfurl in the preparation of silver nanoparticles: physical and chemical methodologies. The former involves the processes of condensation and evaporation within a tube furnace operating at atmospheric pressure. While this method has been successful in producing nanoparticles of diverse materials like Ag, Au, and PbS, it comes with significant limitations, including the demand for substantial space, copious energy sources, and the generation of substantial environmental heat. Alternatively, laser fluence can be employed to fine-tune particle size, boasting the advantage of effecting reactions sans any chemical reagents in the solution. The most prevalent method for fabricating stable, colloidal dispersions in both water and organic solvents revolves around chemical reduction. Commonly utilized reductants include elemental hydrogen, ascorbate, borohydride, and citrate. This process ushers in particle diameters measuring in the nanometer range. Notably, the reduction initiates the formation of silver atoms, which subsequently coalesce into oligomer clusters. Protective agents, such as polymers like PVP, PEG, and PMAA, prove indispensable during the synthesis. The use of the chemical approach empowers the creation of size-controllable nanoparticles, albeit with the reliance on potent organic solvents.

To unravel the intricacies of these nanoparticles, a suite of characterization techniques comes into play. These encompass transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and UV-Vis spectroscopy. Together, these methodologies unveil vital insights into size, shape, dimension, and surface area. For instance, TEM, SEM, and AFM provide precise size measurements, while AFM charts the terrain in intricate 3D detail. X-ray diffraction uncovers crystallinity, and UV-Vis spectroscopy unravels the captivating world of Plasmon resonance (Çeşmeli and Biray Avci, 2019).

As the specter of SARS-CoV-2 continues to cast a long shadow over the globe, the quest for defenses intensifies. Amidst the protracted timeline of vaccine development, nanotechnology emerges as a silver lining. Nano-based vaccines are in the offing, albeit navigating the labyrinthine landscape of regulatory clearances. However, nanotechnology has already found its footing in the form of disinfectants and viral detection tools, promising effective countermeasures. Notably, nanoscale sensors are leveraged for the early diagnosis of COVID-19 (Chacón-Torres et al., 2020).

In the quest for innovative ways to curb viral transmission, researchers explore the modification of ventilation system air filters using silver nanoparticles. This groundbreaking endeavor seeks to unravel the extent of their impact on viral disinfection. The utilization of Ag NPs promises to foster highly effective sterile systems, particularly in medical facilities (Chen and Mao, 2007)

5. Silver-based Fabrics

In the realm of pathogen mitigation, human beings emerge as both the primary risk and the ultimate defense. To counteract this delicate equilibrium, advanced technology rooted in silver (Ag) is seamlessly integrated into polycotton fabrics through the meticulous dry pad cure methods. These pioneering techniques have garnered recognition for their remarkable effectiveness in thwarting the spread of coronaviruses. The outcome is nothing short of extraordinary, with a pathogen suppression rate of 99.99%, effectively curbing the peril of cross-infection and allergies, rendering these fabrics unequivocally safe for use. The limelight is now firmly fixed upon the development of materials endowed with the extraordinary ability to impede the transmission, diffusion, and infiltration of pathogens. As the world grapples with the pressing need for personal protective measures, the deployment of cutting-edge solutions assumes paramount importance. The World Health Organization (WHO), attuned to this imperative, has recently championed the universal use of facemasks. At the heart of this transformative narrative lies the marvel of nanotechnology, which meticulously transforms the Ag cation and metal into the nano dimension. This miniaturization heralds a new era in the battle against pathogenic adversaries. Silver nanoparticles (Ag NPs), the shining jewels in this nanotechnological crown, have emerged as formidable combatants against lethal viruses and microorganisms. Their antimicrobial prowess finds a diverse array of applications within textile industries, positioning them as indispensable assets in the ongoing quest for a safer and healthier world.

Silver-based fabrics play a critical role in the battle against COVID-19 due to their exceptional properties and effectiveness in curtailing the spread of the virus. These fabrics, infused with silver (Ag) technology, serve as powerful tools in infection control. One of their primary functions is pathogen inhibition. These fabrics have demonstrated an astounding capacity to suppress coronaviruses at an impressive rate of 99.99%. This inhibition is essential in breaking the transmission chain and preventing cross-infection, a pivotal aspect of managing the COVID-19 pandemic. Moreover, silver-based fabrics act as a formidable defense mechanism. By their very nature, they serve as barriers, intercepting and deactivating pathogens that come into contact with the fabric. This is particularly significant in settings where close human interactions are unavoidable, such as healthcare facilities, public transportation, and high-traffic areas. Additionally, they offer a layer of personal protection. In a world where face masks and personal protective equipment are increasingly vital, these fabrics provide an added level of defense for individuals, contributing to the broader strategy of reducing viral transmission. Furthermore, the deployment of nanotechnology to incorporate silver into these fabrics represents a cutting-edge approach. Nanoscale silver particles, or silver nanoparticles, have proven their efficacy against various viruses and microorganisms, making them a formidable weapon in the fight against COVID-19. Silver-based fabrics serve as a robust defense against COVID-19 by inhibiting pathogen transmission, preventing cross-infection, offering personal protection, and harnessing the power of nanotechnology to enhance their antiviral capabilities. Their role is pivotal in safeguarding public health and reducing the impact of this global health crisis.

6. Investigating the Efficacy of Silver Nanoparticles Against SARS-CoV-2

Silver (Ag) has emerged as a formidable adversary against the SARS-CoV-2 virus, demonstrating its capacity not only to neutralize but also to inhibit its virulent action. The versatility of silver nanoparticles (AgNPs) is witnessed in a spectrum of microbicides designed for biological surfaces, including innovative applications in wound dressings, medical devices, sprays, and advanced fabrics. Colloidal silver has undergone rigorous testing, affirming its potent activity against SARS. AgNPs, with their infinitesimal particle size, wield a profound impact against this viral adversary. They orchestrate their antiviral effects by engaging with viral nucleic acids, exerting an intracellular influence that mitigates the virus's virulence (Cooney, 2020).

The silver nanoparticles' antiviral prowess is not limited to the realm of SARS alone but extends to its broader coronaviral family, making them promising candidates for countering COVID-19. The effectiveness of AgNPs is observed across a spectrum of concentrations and nanoparticle diameters, ranging from 10nm, an ideal range to combat SARS-CoV-2, down to 1-10nm. Beyond this window of antiviral efficiency, cytotoxic effects are observed at concentrations surpassing 20 ppm. Intriguingly, AgNPs employ a sophisticated disruption tactic, as revealed by Luciferase-based pseudo-virus assays. Their action hinges on infiltrating the virus's integrity, thwarting its entry into host cells. Despite their remarkable potential against SARS-CoV-2, the deployment of AgNPs demands judicious caution due to their environmental implications and potential toxicity, underscoring the vital need for responsible usage (Cunningham et al., 2018).

7. Silver Respi-Strip: Pioneering COVID-19 Detection

The Ag Respi-Strips stand as exemplars of cutting-edge immune-chromatographic assays (ICT) meticulously designed for the swift and precise identification of COVID-19 in afflicted individuals. These remarkable diagnostic tools are firmly rooted in advanced membrane technology, bolstered by the results of rigorous analytical and clinical studies encompassing approximately 400 observations. The Respi-Strips themselves are composed of nitrocellulose and colloidal gold conjugates, two components that synergistically enable the detection of the virus. Monoclonal antibodies, strategically engineered to target the SARS-CoV-2 virus, feature prominently in these strips, serving as the linchpin of their diagnostic prowess. To initiate the COVID-19 Ag strip test, a mere 100μL sample is introduced into a collection tube, followed by the addition of a dilution buffer in a 1:2 ratio. This buffer, comprising key elements such as EDTA, NaN3, and a potent blocking agent, also incorporates a detergent to facilitate the process. The capped tube is gently agitated, allowing the reaction to unfold over a span of 15 minutes. The results of this diagnostic ballet are strikingly discernible.

In the event of a negative response, a reddish-purple hue conspicuously emerges at the control line. However, in the case of positive results, a resplendent purple color graces not only the control line but also the test line, providing an unmistakable visual indicator of the virus's presence. The outcome of this comprehensive study underscores the remarkable attributes of the Respi-Strips, showcasing their capacity for reproducibility at an impressive 1.7%, an astounding robustness of 98%, and a notable absence of cross-reactivity. In the clinical domain, where efficacy is paramount, these strips have demonstrated a sensitivity of 57.6%, a specificity of 99.5%, and an overall diagnostic accuracy of 82.6% during the ascending phase of the epidemic, firmly establishing their role as a powerful tool in the ongoing battle against COVID-19 (Ernst et al., 2019).

8. Unlocking the Potential of Titanium Dioxide Nanoparticles

In the realm of nanotechnology, nanoparticles (NPs) have ascended to prominence, finding multifaceted applications as antibacterial materials, essential components of cosmetics, sophisticated drug delivery systems, integral constituents of advanced electronics, and even indispensable components of sunscreens (Robertson et al., 2010). Nanoparticles, the minuscule powerhouses of this burgeoning field, typically measure between 1 to 100 nanometers in size, underscoring their exquisite precision (Gloag et al., 2019). Among the pantheon of nanoparticles, titanium dioxide emerges as a molecular marvel, composed of a single titanium atom married to two oxygen atoms. This versatile substance exists in various incarnations, often assuming the form of nanocrystals or nanodots, each distinguished by its remarkable surface area and attendant properties. Notably, titanium dioxide is a metal oxide that finds its origin in the natural world, where it exists in three primary forms: anatase, rutile, and brookite (Gupta and Tripathi, 2011).

A defining attribute of titanium dioxide nanoparticles is their photoreactivity, imbuing them with the remarkable capacity to harness light energy, even at reduced temperatures, to catalyze reactions with other molecules. While numerous photocatalytic materials jostle for attention, researchers have identified titanium dioxide as a standout performer, particularly when exposed to the illuminating embrace of sunlight. Furthermore, the stability of titanium dioxide nanoparticles is intricately linked to temperature and pressure. Notably, anatase and brookite, under the influence of heat, metamorphose into the more stable rutile phase, a testament to their adaptability (Horikoshi and SERPONE, 2013). The synthesis of these nanoparticles unfolds through an array of sophisticated techniques, including the Sol-Gel Process, Reverse Micelles, Gas Phase (Aerosol) Synthesis (Pratsinis, 2011), the Metal Organic Chemical Vapor Deposition (MOCVD) (Islam and Ahsan, 2020), and wet chemical synthesis via the precipitation of hydroxides from salts. Additionally, microemulsion-mediated methods play a pivotal role in the fabrication of these remarkable nanoscale structures (Chhabra et al., 1995). As the narrative of nanotechnology continues to evolve, the versatile nature of titanium dioxide nanoparticles stands as a testament to their potential for groundbreaking innovations and applications in this dynamic field.

9. Exploring the Potential of Titanium Dioxide Nanoparticles in SARS-CoV-2 Detection and Beyond

The precision and accuracy with which biomarkers can be detected are instrumental in the effectiveness of electrochemical biosensors, making them invaluable in the realm of biomolecule sensing. These electrochemical biosensors have proven their mettle in the detection of numerous viruses, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (Jeremiah et al., 2020; Kaur et al., 2014), the Human Influenza A Virus H9N2 (Sayhi et al., 2018), and the Human Enterovirus 71 EV71 (Hou et al., 2018). Further expanding the horizons, research has demonstrated that biomarkers associated with tuberculosis can be accurately detected through the deployment of Co-functionalized titanium dioxide nanotubes (Ni-TNTs) (Bhattacharyya et al., 2016). In this intricate mechanism, a complex emerges between cobalt (Co) and the biomarker at a specific preferred voltage, facilitated by the biomarker's oxidation and the reduction of Co-ions. This insight leads to a tantalizing hypothesis that, if a complex could be formed between these functionalized nanoparticles and the Spike Receptor-Binding Domain (S-RBD) protein of SARS-CoV-2, then an electrochemical sensor could effectively detect the virus. Indeed, the S-RBD protein becomes the pivotal point of focus, and a Co-functionalized Titanium Dioxide Nanotube (Co-TNTs) based electrochemical sensor emerges as a potentially effective means of SARS-CoV-2 detection (Vadlamani et al., 2020).

Titanium dioxide nanoparticles, renowned for their antiviral properties, have previously exhibited remarkable efficacy against the Influenza Virus (Nakano et al., 2012), a pathogen that shares several similarities with the causative agent of COVID-19. Significantly, the Photocatalytic Titanium Apatite Filter has demonstrated the capability to inactivate SARS Coronavirus by up to 99.99% (Han et al., 2004). With a striking parallel, Nano-sized Titanium Dioxide (TNPs) coatings under UV exposure have shown the potential to inactivate Human Coronavirus HCoV-NL63, opening up the tantalizing possibility that such coatings could enhance virus inactivation for SARS-CoV-2 (Khorsandi et al., 2021). This hypothesis finds its basis in the structural similarities between HCoV-NL63 and SARS-CoV-2, both of which trigger respiratory diseases (Xia et al., 2020).

Beyond its vital role in virus detection, titanium dioxide serves as an indispensable pigment recognized as Titanium White, Pigment White 6, or CI 77891. A significant milestone in the early twentieth century was the large-scale production of titanium dioxide, which emerged as a nontoxic alternative to traditional white dyes for paints (Ziental et al., 2020). Presently, its applications encompass an array of sectors, including plastics, the pharmaceutical industry, cosmetics (particularly sunscreens), and the food industry where it plays the role of a nontoxic pigment (Carp et al., 2004). Notably, titanium dioxide nanoparticles have carved out a niche in various medical domains, with applications ranging from their use as photosensitizers in Photodynamic Therapy (PDT) to their deployment in Sonodynamic Therapy (SDT) and drug delivery systems (Layqah and Eissa, 2019).

10. Iron Nanoparticles: a Potential Arsenal Against COVID-19

Amid the global quest to combat COVID-19, the World Health Organization (WHO) has embarked on a strategy of repurposing existing medications, seeking effective alternatives to quell the pandemic. In this pursuit, iron nanoparticles, notably sanctioned by the FDA for the treatment of anemia, have emerged as a prospective candidate for in vitro applications against COVID-19. A pivotal docking study was conducted to delve into the intricate interactions between Fe2O3 and Fe3O4 nanoparticles and the spike protein receptor binding domain of the SARS-CoV-2 virus. The intriguing findings unveiled a compelling connection, with both iron nanoparticles engaging the glycoprotein membrane. Of noteworthy significance, Fe3O4 exhibited a more robust and stable interaction, while Fe2O3 garnered preference as a favored contender. This interaction between ions and viral proteins bears profound implications, ultimately leading to viral inactivation. Consequently, these iron nanoparticles have been ushered into the spotlight as promising candidates warranting clinical trials, marking a significant stride in the relentless battle against COVID-19 (Abo-Zeid et al., 2020).

11. Magnetic Nanoparticles (MNPs): Versatile Marvels with Broad-Spectrum Applications

Within the realm of nanotechnology, magnetic nanoparticles, or MNPs, have emerged as a category of extraordinary significance. These nanoscale materials, measuring between 50 and 200 nanometers in diameter, are composed of magnetic materials like nickel, cobalt, iron, and copper intricately fused with functional chemical components, granting them a unique set of properties. Notably, MNPs can be manipulated through the application of magnetic fields, rendering them remarkably versatile for a wide array of applications. Their application landscape spans diverse domains, including environmental, clinical, and biomedical applications, each harnessing their distinctive attributes (Ways et al.,2018; Majidi et al., 2016; Unni et al., 2017). In the ongoing COVID-19 pandemic, MNPs have garnered considerable attention for their role in both detection and mitigation efforts. Research has illuminated their potential to not only detect the virus but also combat its spread. These nanoparticles boast a confluence of superparamagnetic behavior and diminutive dimensions comparable to molecular analytes, further amplifying their utility. The lineage of magnetic nanoparticles can be traced back to amorphous alloys, characterized by a high level of anisotropy. Over time, these alloys have been refined, with notable alloys like FINEMET, NANOPERM, and HITPERM exhibiting enhanced magnetic saturation and coercivity (Malekshahi et al., 2013; Mertens et al., 2020; Mohammed et al., 2017). With continuous advancements, researchers have achieved shape-controlled MNPs with narrow size distributions, employing diverse synthesis methods such as co-precipitation, microemulsion, thermal decomposition, combustion, solvothermal, sonochemical, and flame spray pyrolysis (Majidi et al., 2016). The precision in physical size and shape control is remarkable in these methods, although magnetic property control lags comparatively.

Magnetic nanoparticles have forged a significant presence across various domains, including biotechnology, material science, environmental applications, and beyond (Akbarzadeh et al., 2012). They excel in sensing applications, offering solutions for challenging issues like lower detection limits and nonspecific effects (Šafařík and Šafaříková, 2002; Williams, 2017; Gloag et al., 2019). Furthermore, they present immense promise in the realms of drug delivery, hyperthermia cancer treatment, tissue growth, and infection prevention for medical implants (Cunningham et al., 2018; Tran and Webster, 2010). The utility of magnetic separation employing MNPs has been demonstrated in numerous research fields and industries. This approach boasts numerous advantages, including heightened separation efficiency, rapid separation rates, and cost-effectiveness compared to traditional sedimentation or centrifugation techniques (Wang et al., 2019). Notably, MNPs have impacted the petroleum industry, offering capabilities for targeted adsorption, remote detection, directional transport, and local heating (Shahidi, 2021). The broad scope of MNPs extends to applications in textiles, environmental endeavors, wastewater treatment, genetics, and surface engineering (Ernst et al., 2019; Kaur et al., 2014). In sum, the multifaceted applications of magnetic nanoparticles have ushered in a new era of innovation, promising advancements and solutions in a multitude of fields.

12. Magnetic Nanoparticles in the Battle Against COVID-19

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has profoundly impacted global healthcare systems and economic stability. In the quest to curb the virus's relentless spread and implement effective control strategies, expedient and precise diagnostics play a pivotal role. The global scientific community, both in academia and industry, has embarked on an exhaustive journey, blending cutting-edge research with advanced technologies to counteract the health crisis. Amid these multifaceted efforts, nanoscience and nanotechnology have come to the fore, offering a promising avenue to enhance sensitivity, speed, and reliability in diagnostics and therapeutic options, not only for COVID-19 but for any future outbreaks (Wu et al., 2020; Campos et al., 2020; Ruiz-Hitzky et al., 2020; Talebian et al., 2020).

At the forefront of these innovative strategies is magnetic nano-sensing, representing the intersection of modern biosensing and magnetic technologies. Over recent years, magnetic tools have made remarkable inroads in biological and biomedical applications, poised to revolutionize the diagnostics landscape. The promise lies in their potential to transform labor-intensive and costly diagnostics into user-friendly, cost-effective protocols, while offering superior or at least equivalent sensitivity. Such a shift could significantly bolster the surveillance and management of coronavirus infections within populations (Wu et al., 2020; Campos et al., 2020; Ruiz-Hitzky et al., 2020).

In the context of COVID-19, magnetic nanoparticles (MNPs) have assumed a critical role, particularly in diagnostic applications. They enable fully automated nucleic acid purification, a crucial step in SARS-CoV-2 diagnosis (Islam, and Ahsan, 2020). Through innovative methodologies, a magnetic field, facilitated by nontoxic MNPs, can effectively neutralize key viral components, such as +ssRNA, M (membrane) protein, and the spike protein present in SARS-CoV-2. Magnetic tweezers, an instrument capable of generating magnetic traps, employ nontoxic MNPs as magnetic beads to manipulate +ssRNA orientation and disrupt the spike protein (Islam, and Ahsan, 2020). One of the most notable methods for COVID-19 detection involves real-time RT-PCR combined with the use of functionalized magnetic nanoparticles for rapid extraction and purification of viral RNA from nasopharyngeal cells. This streamlined process integrates lysis and binding steps into a single procedure, permitting the direct introduction of magnetic nanoparticle-RNA complexes into subsequent RT-PCR reactions. The efficiency of this method is evident in its capacity to purify viral RNA from multiple samples within a mere 20 minutes, employing either manual or high-throughput automated techniques. The method has achieved a 10-copy sensitivity and a robust linear correlation over a broad range of viral RNA copies (10 to 100,000 copies of SARS-CoV-2 pseudo-viral particles) (Chacón-Torres et al., 2020; Zhao et al., 2020). However, this technique necessitates specialized magnetic nanoparticles characterized by a strong negative charge for efficient viral RNA extraction. In this quest, zinc ferrite nanoparticles have also been utilized to streamline RNA extraction, offering a highly efficient protocol with a remarkable reduction in operation time and requirements (Somvanshi et al., 2020; Nikolaeva-Glomb et al., 2017). Collaboration between researchers from NTNU’s Department of Clinical and Molecular Medicine and the Department of Chemical Engineering has yielded an in-house chemical mix combined with NTNU-crafted magnetic nanoparticles, constituting an effective test method (NTNU, 2020). In the relentless pursuit of a cure, scientists are harnessing the power of nanotechnology for vaccine development. Nanotechnology has also demonstrated its potential to enhance the efficacy of antiviral drugs by surmounting their low bioavailability. Notably, the development of nanomaterials, such as nanogels, capable of capturing viable virus particles and viral RNA/proteins, is promising. Additionally, lipid nanoparticles, acting as protective molecular envelopes for mRNA strands, are enabling advanced technologies in vaccines and drug delivery, circumventing biological barriers and delivering their cargo to target cells effectively (Campos et al., 2020; Rabiee et al., 2020)

13. Gold Nanoparticles (AuNPs): Shaping the Future of Biomedical Advancements

Gold nanoparticles, often bearing the mesmerizing hue of fine wine, are far more than just visually appealing compounds. They encompass a diverse spectrum of sizes, spanning from a mere 1 nanometer to a substantial 8 micrometers. The significance of gold nanoparticles (AuNPs) transcends their aesthetic charm, primarily owing to their profound implications in the realms of biomedicine, drug delivery, biosensors, and their remarkable antioxidant and anticancer attributes. What sets them apart is their distinctive blend of biocompatibility, well-defined geometry, steadfast stability, and the ease with which they can be synthesized (Mokammel et al., 2019; Saei et al., 2020). The remarkable antibacterial properties of gold nanoparticles can be traced back to their ability to generate reactive oxygen species (ROS), which unleash oxidative havoc within microbial cells. Furthermore, when subjected to laser irradiation, AuNPs harness this energy to produce heat through the excitation of electrons. This dual nature of AuNPs makes them exceedingly versatile, capable of serving as both potent anticancer warriors and formidable antibacterial agents (Mokammel et al., 2019).

The synthesis of AuNPs is a multifaceted process, with various methods at our disposal. These shimmering particles can be crafted through chemical, Turkevich, Brust-Schiffrin, electrochemical, seeding growth, and biological techniques. In the realm of biological applications, colloidal synthesis reigns supreme as the method of choice (Herizchi et al., 2016; Kong et al., 2017). AuNPs, endowed with photosensitivity, harbor a degree of radioactivity, thanks to their higher atomic number. Their smaller counterparts, those measuring less than 2 nanometers, exert cellular oxidative stress, inflict mitochondrial damage, and engage in intricate DNA interactions to obliterate cancer cells. Additionally, AuNPs wield the power to quench fluorescence (Yeh et al., 2012). But the allure of AuNPs doesn't stop there. They can be employed in the production of antibodies (Dykman and Khlebtsov, 2017). In the context of drug delivery (Saha et al., 2007; Ghosh et al., 2008; Sundresh, 2013), they play a pivotal role. Here, drug delivery emerges as a precision process, orchestrating the release of biologically active compounds at designated rates and specific locations. Their utility extends to gene delivery (Kim et al., 2012), as well as the delivery of proteins and vaccines. Furthermore, AuNPs become instrumental in antibody labeling (Tvrdonova et al., 2019), electrochemical sensing of antigens, and the diagnosis of various ailments, most notably those associated with cancer and viral infections (Boisselier and Astruc, 2009)

14. AuNPs and Their Role in Combating COVID-19

Gold nanoparticles (AuNPs) have steadily surged to prominence within the realm of biomedical and diagnostic applications (Draz and Shafiee, 2018). The urgent need to detect SARS-CoV-2, the virus behind COVID-19, has harnessed the unique attributes of AuNPs. Employing the localized surface plasmon resonance (LSPR) principle, AuNPs are coupled with antisense oligonucleotides (ASOs) targeting the viral N-gene. Detection hinges upon the aggregation of AuNPs catalyzed by the viral N-gene, an observation made possible through colorimetric detection (Moitra et al., 2020; Li and Rothberg, 2004; Silveyra et al., 2011). Pioneering strides are being made in the race for efficient diagnostics. Scientists at the University of Maryland School of Medicine have ingeniously crafted a cost-effective experimental diagnostic test, providing rapid and visual identification of COVID-19 virus presence (Teirumnieks et al., 2020; Tremiliosi et al., 2020). The test relies on a straightforward assay, blending a liquid solution with plasmonic gold nanoparticles, each adorned with a highly-specific molecule for detecting COVID-19 proteins. A saliva sample or nasal swab from a patient is introduced to the assay, and the solution is observed for any telltale color shift. The shift is a transition from purple to a deep blue, signifying the presence of COVID-19 proteins. A notable advantage of this test is its ability to be administered without the need for highly trained personnel or advanced laboratory setups (University of Maryland School of Medicine).

Gold nanoparticles, revered for their interactions with viruses and capacity to thwart cellular entry, wield a potent blend of a high specific surface area and the flexibility to be functionalized with an array of functional groups. These nanoparticles are proficient not only in delivering therapeutic peptides to specific cell surface receptors, thereby activating intracellular pathways, but also in the conveyance of larger biomolecules such as DNA, RNA, peptides, and proteins. They exhibit a remarkable capacity for blocking viral entry into host cells while maintaining low toxicity (Medhi et al., 2020; Tabish and Hamblin, 2020). In essence, these virtuous metal-based nanoparticles act as viral gatekeepers, foiling the virus's entry into host cells. Their innate ability to access cells via endocytosis, coupled with their proficiency in interacting with viral proteins, makes them a powerful arsenal in the battle against viral genome replication (Vijayakumar and Ganesan, 2012).

AuNPs have emerged as pivotal components in vaccine development, igniting strong IgG responses when tested on mice, especially for the SARS-CoV S protein (Sekimukai et al., 2020; Tadic et al., 2014). Furthermore, evaluations of protective immune responses induced by gold nanoparticles (AuNPs) conjugated with the swine transmissible gastroenteritis virus (TGEV) revealed promising results in mice and rabbits (Staroverov et al., 2011). Thus, AuNPs, in conjunction with viruses, stand as potential antiviral candidates for future SAR-CoV-2 vaccine applications. Beyond diagnostics and immunogenic agents, gold nanoparticles hold the promise of mitigating gastrointestinal tract reactions triggered by COVID-19 (Ways et al., 2018). Their utility transcends pandemics, making them formidable antiviral agents effective against a spectrum of viruses, including SARS-CoV-2, albeit with the requirement for further research (Ways et al., 2018). In the future, it's anticipated that AuNPs, and nanoparticles in general, will wield a pivotal role in the fight against COVID-19.

15. Conclusion

Nanoparticles, the minute marvels with their diverse compositions encompassing iron, titanium, silver, gold, and magnetic variants (as depicted in Figure 1), assume a pivotal and cohesive role in the ongoing crusade against infections. Notably, magnetic nanoparticles exhibit an innate susceptibility to magnetic field manipulation, a characteristic skillfully harnessed within the biomedical sector. Their multifaceted contributions to vaccine development and detection merit profound acknowledgment. Among these, the Ag Respi strips stand out, delivering superlative test results, heralding a breakthrough in our fight against infections. Furthermore, the utilization of iron nanoparticles emerges as a promising avenue for infection treatment. This cutting-edge textile material emerges as a formidable safeguard, orchestrating an extraordinary defense against the onslaught of infectious agents. As we delve deeper into the nuanced realm of nanoparticles, their potential to reshape our approach to infection management becomes increasingly evident.

Figure 1
Nanobiotechnological strategies targeting SARS-CoV-2.

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Publication Dates

• Publication in this collection
  27 Jan 2025
• Date of issue
  2024

History

• Received
  16 Oct 2023
• Accepted
  16 May 2024