Nanotechnology-Enabled Biosensors: A Review of Fundamentals, Design Principles, Materials, and Applications.

Biosensors are modern engineering tools that can be widely used for various technological applications. In the recent past, biosensors have been widely used in a broad application spectrum including industrial process control, the military, environmental monitoring, health care, microbiology, and food quality control. Biosensors are also used specifically for monitoring environmental pollution, detecting toxic elements' presence, the presence of bio-hazardous viruses or bacteria in organic matter, and biomolecule detection in clinical diagnostics. Moreover, deep medical applications such as well-being monitoring, chronic disease treatment, and in vitro medical examination studies such as the screening of infectious diseases for early detection. The scope for expanding the use of biosensors is very high owing to their inherent advantages such as ease of use, scalability, and simple manufacturing process. Biosensor technology is more prevalent as a large-scale, low cost, and enhanced technology in the modern medical field. Integration of nanotechnology with biosensors has shown the development path for the novel sensing mechanisms and biosensors as they enhance the performance and sensing ability of the currently used biosensors. Nanoscale dimensional integration promotes the formulation of biosensors with simple and rapid detection of molecules along with the detection of single biomolecules where they can also be evaluated and analyzed critically. Nanomaterials are used for the manufacturing of nano-biosensors and the nanomaterials commonly used include nanoparticles, nanowires, carbon nanotubes (CNTs), nanorods, and quantum dots (QDs). Nanomaterials possess various advantages such as color tunability, high detection sensitivity, a large surface area, high carrier capacity, high stability, and high thermal and electrical conductivity. The current review focuses on nanotechnology-enabled biosensors, their fundamentals, and architectural design. The review also expands the view on the materials used for fabricating biosensors and the probable applications of nanotechnology-enabled biosensors.

Nanotechnology-Assisted Biosensors for the Detection of Viral Nucleic Acids: An Overview.

The accurate and rapid diagnosis of viral diseases has garnered increasing attention in the field of biosensors. The development of highly sensitive, selective, and accessible biosensors is crucial for early disease detection and preventing mortality. However, developing biosensors optimized for viral disease diagnosis has several limitations, including the accurate detection of mutations. For decades, nanotechnology has been applied in numerous biological fields such as biosensors, bioelectronics, and regenerative medicine. Nanotechnology offers a promising strategy to address the current limitations of conventional viral nucleic acid-based biosensors. The implementation of nanotechnologies, such as functional nanomaterials, nanoplatform-fabrication techniques, and surface nanoengineering, to biosensors has not only improved the performance of biosensors but has also expanded the range of sensing targets. Therefore, a deep understanding of the combination of nanotechnologies and biosensors is required to prepare for sanitary emergencies such as the recent COVID-19 pandemic. In this review, we provide interdisciplinary information on nanotechnology-assisted biosensors. First, representative nanotechnologies for biosensors are discussed, after which this review summarizes various nanotechnology-assisted viral nucleic acid biosensors. Therefore, we expect that this review will provide a valuable basis for the development of novel viral nucleic acid biosensors.

Advances and opportunities in nanoimaging agents for the diagnosis of inflammatory lung diseases.

The development of rapid, noninvasive diagnostics to detect lung diseases is a great need after the COVID-2019 outbreak. The nanotechnology-based approach has improved imaging and facilitates the early diagnosis of inflammatory lung diseases. The multifunctional properties of nanoprobes enable better spatial-temporal resolution and a high signal-to-noise ratio in imaging. Targeted nanoimaging agents have been used to bind specific tissues in inflammatory lungs for early-stage diagnosis. However, nanobased imaging approaches for inflammatory lung diseases are still in their infancy. This review provides a solution-focused approach to exploring medical imaging technologies and nanoprobes for the detection of inflammatory lung diseases. Prospects for the development of contrast agents for lung disease detection are also discussed.

Spotlight on mycobacterial lipid exploitation using nanotechnology for diagnosis, vaccines, and treatments.

Tuberculosis (TB), historically the most significant cause of human morbidity and mortality, has returned as the top infectious disease worldwide, under circumstances worsened by the COVID-19 pandemic's devastating effects on public health. Although Mycobacterium tuberculosis, the causal agent, has been known of for more than a century, the development of tools to control it has been largely neglected. With the advancement of nanotechnology, the possibility of engineering tools at the nanoscale creates unique opportunities to exploit any molecular type. However, little attention has been paid to one of the major attributes of the pathogen, represented by the atypical coat and its abundant lipids. In this review, an overview of the lipids encountered in M. tuberculosis and interest in exploiting them for the development of TB control tools are presented. Then, the amalgamation of nanotechnology with mycobacterial lipids from both reported and future works are discussed.

Recent Development in Plasmonic Nanobiosensors for Viral DNA/RNA Biomarkers.

Recently, due to the coronavirus pandemic, the need for early diagnosis of infectious diseases, including viruses, is emerging. Though early diagnosis is essential to prevent infection and progression to severe illness, there are few technologies that accurately measure low concentrations of biomarkers. Plasmonic nanomaterials are attracting materials that can effectively amplify various signals, including fluorescence, Raman, and other optical and electromagnetic output. In this review, we introduce recently developed plasmonic nanobiosensors for measuring viral DNA/RNA as potential biomarkers of viral diseases. In addition, we discuss the future perspective of plasmonic nanobiosensors for DNA/RNA detection. This review is expected to help the early diagnosis and pathological interpretation of viruses and other diseases.

Narrative review on century of respiratory pandemics from Spanish flu to COVID-19 and impact of nanotechnology on COVID-19 diagnosis and immune system boosting.

The rise of the highly lethal severe acute respiratory syndrome-2 (SARS-2) as corona virus 2019 (COVID-19) reminded us of the history of other pandemics that happened in the last century (Spanish flu) and stayed in the current century, which include Severe-Acute-Respiratory-Syndrome (SARS), Middle-East-Respiratory-Syndrome (MERS), Corona Virus 2019 (COVID-19). We review in this report the newest findings and data on the origin of pandemic respiratory viral diseases, reservoirs, and transmission modes. We analyzed viral adaption needed for host switch and determinants of pathogenicity, causative factors of pandemic viruses, and symptoms and clinical manifestations. After that, we concluded the host factors associated with pandemics morbidity and mortality (immune responses and immunopathology, ages, and effect of pandemics on pregnancy). Additionally, we focused on the burdens of COVID-19, non-pharmaceutical interventions (quarantine, mass gatherings, facemasks, and hygiene), and medical interventions (antiviral therapies and vaccines). Finally, we investigated the nanotechnology between COVID-19 analysis and immune system boosting (Nanoparticles (NPs), antimicrobial NPs as antivirals and immune cytokines). This review presents insights about using nanomaterials to treat COVID-19, improve the bioavailability of the abused drugs, diminish their toxicity, and improve their performance.

The Promise of Emergent Nanobiotechnologies for In Vivo Applications and Implications for Safety and Security.

Nanotechnology, the multidisciplinary field based on the exploitation of the unique physicochemical properties of nanoparticles (NPs) and nanoscale materials, has opened a new realm of possibilities for biological research and biomedical applications. The development and deployment of mRNA-NP vaccines for COVID-19, for example, may revolutionize vaccines and therapeutics. However, regulatory and ethical frameworks that protect the health and safety of the global community and environment are lagging, particularly for nanotechnology geared toward biological applications (ie, bionanotechnology). In this article, while not comprehensive, we attempt to illustrate the breadth and promise of bionanotechnology developments, and how they may present future safety and security challenges. Specifically, we address current advancements to streamline the development of engineered NPs for in vivo applications and provide discussion on nano-bio interactions, NP in vivo delivery, nanoenhancement of human performance, nanomedicine, and the impacts of NPs on human health and the environment.

Recombinant protein polymer-antibody conjugates for applications in nanotechnology and biomedicine.

Currently, there are over 100 antibody-based therapeutics on the market for the treatment of various diseases. The increasing importance of antibody treatment is further highlighted by the recent FDA emergency use authorization of certain antibody therapies for COVID-19 treatment. Protein-based materials have gained momentum for antibody delivery due to their biocompatibility, tunable chemistry, monodispersity, and straightforward synthesis and purification. In this review, we discuss progress in engineering the molecular features of protein-based biomaterials, in particular recombinant protein polymers, for introducing novel functionalities and enhancing the delivery properties of antibodies and related binding protein domains.

Nanotechnology Transition Roadmap toward Multifunctional Stimuli-Responsive Face Masks.

In recent times, the use of personal protective equipment, such as face masks or respirators, is becoming more and more critically important because of common pollution; furthermore, face masks have become a necessary element in the global fight against the COVID-19 pandemic. For this reason, the main mission of scientists has become the development of face masks with exceptional properties that will enhance their performance. The versatility of electrospun polymer nanofibers has determined their suitability as a material for constructing "smart" filter media. This paper provides an overview of the research carried out on nanofibrous filters obtained by electrospinning. The progressive development of the next generation of face masks whose unique properties can be activated in response to a specific external stimulus is highlighted. Thanks to additional components incorporated into the fiber structure, filters can, for example, acquire antibacterial or antiviral properties, self-sterilize the structure, and store the energy generated by users. Despite the discovery of several fascinating possibilities, some of them remain unexplored. Stimuli-responsive filters have the potential to become products of large-scale availability and great importance to society as a whole.

Nanotechnology and COVID-19 Convergence: Toward New Planetary Health Interventions Against the Pandemic.

COVID-19 is a systemic disease affecting multiple organ systems and caused by infection with the SARS-CoV-2 virus. Two years into the COVID-19 pandemic and after the introduction of several vaccines, the pandemic continues to evolve in part owing to global inequities in access to preventive and therapeutic measures. We are also witnessing the introduction of antivirals against COVID-19. Against this current background, we review the progress made with nanotechnology-based approaches such as nanoformulations to combat the multiorgan effects of SARS-CoV-2 infection from a systems medicine lens. While nanotechnology has previously been widely utilized in the antiviral research domain, it has not yet received the commensurate interest in the case of COVID-19 pandemic response strategies. Notably, SARS-CoV-2 and nanomaterials are similar in size ranging from 50 to 200 nm. Nanomaterials offer the promise to reduce the side effects of antiviral drugs, codeliver multiple drugs while maintaining stability in the biological milieu, and sustain the release of entrapped drug(s) for a predetermined time period, to name but a few conceivable scenarios, wherein nanotechnology can enable and empower preventive medicine and therapeutic innovations against SARS-CoV-2. We conclude the article by underlining that nanotechnology-based interventions warrant further consideration to enable precision planetary health responses against the COVID-19 pandemic.

Regulatory safety evaluation of nanomedical products: key issues to refine.

Nanotechnologies enable great opportunities for the development and use of innovative (nano)medicines. As is common for scientific and technical developments, recognized safety evaluation methods for regulatory purposes are lagging behind. The specific properties responsible for the desired functioning also hamper the safety evaluation of such products. Pharmacokinetics determination of the active pharmaceutical ingredient as well as the nanomaterial component is crucial. Due to their particulate nature, nanomedicines, similar to all nanomaterials, are primarily removed from the circulation by phagocytizing cells that are part of the immune system. Therefore, the immune system can be potentially a specific target for adverse effects of nanomedicines, and thus needs special attention during the safety evaluation. This DDTR special issue on the results of the REFINE project on a regulatory science framework for nanomedical products presents a highly valuable body of knowledge needed to address regulatory challenges and gaps in currently available testing methods for the safety evaluation of nanomedicines.

Virus-like Particles: Fundamentals and Biomedical Applications.

Nanotechnology is a fast-evolving field focused on fabricating nanoscale objects for industrial, cosmetic, and therapeutic applications. Virus-like particles (VLPs) are self-assembled nanoparticles whose intrinsic properties, such as heterogeneity, and highly ordered structural organization are exploited to prepare vaccines; imaging agents; construct nanobioreactors; cancer treatment approaches; or deliver drugs, genes, and enzymes. However, depending upon the intrinsic features of the native virus from which they are produced, the therapeutic performance of VLPs can vary. This review compiles the recent scientific literature about the fundamentals of VLPs with biomedical applications. We consulted different databases to present a general scenario about viruses and how VLPs are produced in eukaryotic and prokaryotic cell lines to entrap therapeutic cargo. Moreover, the structural classification, morphology, and methods to functionalize the surface of VLPs are discussed. Finally, different characterization techniques required to examine the size, charge, aggregation, and composition of VLPs are described.

Nanotechnology-based strategies against SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already infected more than 500 million people globally (as of May 2022), creating the coronavirus disease 2019 (COVID-19) pandemic. Nanotechnology has played a pivotal role in the fight against SARS-CoV-2 in various aspects, with the successful development of the two highly effective nanotechnology-based messenger RNA vaccines being the most profound. Despite the remarkable efficacy of mRNA vaccines against the original SARS-CoV-2 strain, hopes for quickly ending this pandemic have been dampened by the emerging SARS-CoV-2 variants, which have brought several new pandemic waves. Thus, novel strategies should be proposed to tackle the crisis presented by existing and emerging SARS-CoV-2 variants. Here, we discuss the SARS-CoV-2 variants from biological and immunological perspectives, and the rational design and development of novel and potential nanotechnology-based strategies to combat existing and possible future SARS-CoV-2 variants. The lessons learnt and design strategies developed from this battle against SARS-CoV-2 variants could also inspire innovation in the development of nanotechnology-based strategies for tackling other global infectious diseases and their future variants.

Targeting eosinophils in chronic respiratory diseases using nanotechnology-based drug delivery.

Asthma, COPD, COVID-19, EGPA, Lung cancer, and Pneumonia are major chronic respiratory diseases (or CRDs) affecting millions worldwide and account for substantial morbidity and mortality. These CRDs are irreversible diseases that affect different parts of the respiratory system, imposing a considerable burden on different socio-economic classes. All these CRDs have been linked to increased eosinophils in the lungs. Eosinophils are essential immune mediators that contribute to tissue homeostasis and the pathophysiology of various diseases. Interestingly, elevated eosinophil level is associated with cellular processes that regulate airway hyperresponsiveness, airway remodeling, mucus hypersecretion, and inflammation in the lung. Therefore, eosinophil is considered the therapeutic target in eosinophil-mediated lung diseases. Although, conventional medicines like antibiotics, anti-inflammatory drugs, and bronchodilators are available to prevent CRDs. But the development of resistance to these therapeutic agents after long-term usage remains a challenge. However, progressive development in nanotechnology has unveiled the targeted nanocarrier approach that can significantly improve the pharmacokinetics of a therapeutic drug. The potential of the nanocarrier system can be specifically targeted on eosinophils and their associated components to obtain promising results in the pharmacotherapy of CRDs. This review intends to provide knowledge about eosinophils and their role in CRDs. Moreover, it also discusses nanocarrier drug delivery systems for the targeted treatment of CRDs.

From Prevention to Therapy: A Roadmap of Nanotechnologies to Stay Ahead of Future Pandemics.

Several recent viral outbreaks, culminating in the COVID-19 pandemic, have illustrated the need for comprehensive improvement in the detection, control, and treatment of emerging viruses that exhibit the potential to cause epidemics. Nanotechnology approaches have the potential to make major contributions in all these areas. This perspective is intended to outline how nanotechnology can be employed to improve upon respiratory disease detection and containment measures, and therapeutics, with a particular emphasis on applications that can address key areas, including home diagnostics, contact tracing, and the evaluation of durability of vaccine protection over time and against future variants. Nanotechnology offers potent tools to address these needs, but further research is required to validate these applications to address needs of future epidemics.

Where Is Nano Today and Where Is It Headed? A Review of Nanomedicine and the Dilemma of Nanotoxicology.

Worldwide nanotechnology development and application have fueled many scientific advances, but technophilic expectations and technophobic demands must be counterbalanced in parallel. Some of the burning issues today are the following: (1) Where is nano today? (2) How good are the communication and investment networks between academia/research and governments? (3) Is there any spotlight application for nanotechnology? Nanomedicine is a particular arm of nanotechnology within the healthcare landscape, focused on diagnosis, treatment, and monitoring of emerging (such as coronavirus disease 2019, COVID-19) and contemporary (including diabetes, cardiovascular diseases, neurodegenerative disorders, and cancer) diseases. However, it may only represent the bright side of the coin. In fact, in the recent past, the concept of nanotoxicology has emerged to address the dark shadows of nanomedicine. The nanomedicine field requires more nanotoxicological studies to identify undesirable effects and guarantee safety. Here, we provide an overall perspective on nanomedicine and nanotoxicology as central pieces of the giant puzzle of nanotechnology. First, the impact of nanotechnology on education and research is highlighted, followed by market trends and scientific output tendencies. In the next section, the nanomedicine and nanotoxicology dilemma is addressed through the interplay of in silico, in vitro, and in vivo models with the support of omics and microfluidic approaches. Lastly, a reflection on the regulatory issues and clinical trials is provided. Finally, some conclusions and future perspectives are proposed for a clearer and safer translation of nanomedicines from the bench to the bedside.

Aptamers for Viral Detection and Inhibition.

Recent times have experienced more than ever the impact of viral infections in humans. Viral infections are known to cause diseases not only in humans but also in plants and animals. Here, we have compiled the literature review of aptamers selected and used for detection and inhibition of viral infections in all three categories: humans, animals, and plants. This review gives an in-depth introduction to aptamers, different types of aptamer selection (SELEX) methodologies, the benefits of using aptamers over commonly used antibody-based strategies, and the structural and functional mechanism of aptasensors for viral detection and therapy. The review is organized based on the different characterization and read-out tools used to detect virus-aptasensor interactions with a detailed index of existing virus-targeting aptamers. Along with addressing recent developments, we also discuss a way forward with aptamers for DNA nanotechnology-based detection and treatment of viral diseases. Overall, this review will serve as a comprehensive resource for aptamer-based strategies in viral diagnostics and treatment.

Gires-Tournois Immunoassay Platform for Label-Free Bright-Field Imaging and Facile Quantification of Bioparticles.

Bright-field imaging of nanoscale bioparticles is a challenging task for optical microscopy because the light-matter interactions of bioparticles are weak on conventional surfaces due to their low refractive index and small size. Alternatively, advanced imaging techniques, including near-field microscopy and phase microscopy, have enabled visualization and quantification of the bioparticles, but they require assistance of sophisticated/customized systems and post-processing with complex established algorithms. Here, a simple and fast immunoassay device, Gires-Tournois immunoassay platform (GTIP) is presented, which provides unique color dynamics in response to optical environment changes and thus enables the label-free bright-field imaging and facile quantification of bioparticles using conventional optical microscopy. Bioparticles on GTIP slow down the velocity of reflected light, leading to vivid color change according to the local particle density and maximizing chromatic contrast for high spatial distinguishability. The particle distribution and density on the surface of the resonator are readily analyzed through 2D raster-scanning-based chromaticity analysis. GTIP offers multiscale sensing capability for target analytes that possess different refractive indices and sizes.