Microneedle technology for potential SARS-CoV-2 vaccine delivery.

INTRODUCTION: Microneedle fabrication was conceptualized in the 1970s as devices for painless transdermal drug delivery. The last two decades have seen considerable research and financial investment in this area with SARS-CoV-2 and other vaccines catalyzing their application to in vivo intradermal vaccine delivery. Microneedle arrays have been fabricated in different shapes, geometries, formats, and out of different materials. AREAS COVERED: The recent pandemic has offered microneedle platforms the opportunity to be employed as a vehicle for SARS-CoV-2 vaccine administration. Various modes of vaccination delivery and the potential of microneedle array-based vaccines will be presented, with a specific focus placed on recent SARS-CoV-2 research. The advantages of microneedle-based vaccine administration, in addition to the major hurdles to their en masse implementation, will be examined. EXPERT OPINION: Considering the widely acknowledged disadvantages of current vaccine delivery, such as anxiety, pain, and the requirement for professional administration, a large shift in this research sphere is imminent. The SARS-CoV-2 pandemic has catalyzed the development of alternate vaccination platforms, working to avoid the requirement for mass vaccination centers. As microneedle vaccine patches are transitioning through clinical study phases, research will be required to prepare this technology for a more mass production environment.

Radionuclide Therapy Videos on YouTube as An Educational Material: Has the COVID-19 Pandemic Changed the Quality, Usefulness, and Interaction Features.

Introduction: Current treatment approach aims to achieve greater efficacy with fewer side effects, by targeted cancer therapy as much as possible. Radionuclide therapy is a modality that uses cancer theranostics and is increasingly applied for various cancers as a targeted therapy. YouTube is a preferred tool for obtaining medical information from the internet. This study aims to determine the content quality, level of interaction and usefulness as education material of radionuclide therapy YouTube videos and to reveal the impact of the COVID-19 process on these parameters. Materials and Methods: The keywords were searched on YouTube on August 25, 2018, and May 10, 2021. After removing duplicate and excluded videos, all remaining videos were scored and coded. Results: Majority of the videos were useful educational material. Most of them were high quality. Popularity markers were unrelated to quality level. After COVID, the power index of videos with high JAMA scores increased. The COVID-19 pandemic did not have a negative effect on video features; the quality of the content increased even more after the pandemic. Conclusion: Radionuclide therapy YouTube videos have high-quality content and provide useful education material. The popularity is independent of the content quality. During the pandemic, video quality and usefulness characteristics did not change, while the visibility is increased. We consider YouTube to be an appropriate educational material for patients and healthcare professionals to gain basic knowledge of radionuclide therapy. The Covid-19 pandemic highlighted the power of radionuclide therapy YouTube videos as an educational material.

Recent Development of Supramolecular Cancer Theranostics Based on Cyclodextrins: A Review.

With the development of personalized medical demands for precise diagnosis, rational management and effective cancer treatment, supramolecular theranostic systems have received widespread attention due to their reversibly switchable structures, sensitive response to biological stimuli and integration ability for multiple capabilities in a single platform with a programmable fashion. Cyclodextrins (CDs), benefiting from their excellent characteristics, such as non-toxicity, easy modification, unique host-guest properties, good biocompatibility, etc., as building blocks, serve as an all-purpose strategy for the fabrication of a supramolecular cancer theranostics nanodevice that is capable of biosafety, controllability, functionality and programmability. This review focuses on the supramolecular systems of CD-bioimaging probes, CD-drugs, CD-genes, CD-proteins, CD-photosensitizers and CD-photothermal agents as well as multicomponent cooperation systems with regards to building a nanodevice with functions of diagnosis and (or) therapeutics of cancer treatment. By introducing several state-of-the-art examples, emphasis will be placed on the design of various functional modules, the supramolecular interaction strategies under the fantastic topological structures and the hidden "bridge" between their structures and therapeutic efficacy, aiming for further comprehension of the important role of a cyclodextrin-based nanoplatform in advancing supramolecular cancer theranostics.

Applications of Gold and Silver Nanoparticles in Theranostics.

Nanotechnology sculptures the current scenario of science and technology. The word nano refers 'small' which ranges from 10 to 100 nm in size. Silver and gold nanoparticles can be synthesized at nanoscale and have unique biological properties like antibacterial, antifungal, antiviral, antiparasitic, antiplatelet, anti-inflammatory, and anti-tumor activity. In this mini review, we shall discuss the various applications of silver and gold nanoparticles (AuNPs) in the field of therapy, imaging, biomedical devices and in cancer diagnosis. The usage of silver nanoparticles(AgNPs) in dentistry and dental implants, therapeutic abilities like wound dressings, silver impregnated catheters, ventricular drainage catheters, combating orthopedic infections, and osteointegration will be elaborated. Gold nanoparticles in recent years have garnered large importance in bio medical applications. They are being used in diagnosis and have recently seen a surge in therapeutics. In this mini review, we shall see about the various applications of AuNP and AgNP, and highlight their evolution in theranostics.

Theranostics for COVID-19 Antiviral Drugs: Prospects and Challenges for Worldwide Precision/Personalized Medicine.

Coronavirus disease 2019 (COVID-19) is a systemic disease that impacts multiple organ systems with a complex clinical presentation and outcomes that can vary from person to person and between populations. To optimize COVID-19 treatment outcomes, and in light of the availability of antiviral drugs, there is a need for greater attention to the field of theranostics, the fusion of therapeutics and diagnostics. Theranostics tests would be invaluable, we suggest in this expert review, so as to optimize the efficacy and safety of current and future antiviral drugs against COVID-19. Theranostics would also assist in the design and implementation of clinical trials with antiviral drug candidates. We discuss here theranostics considering drugs such as remdesivir, Paxlovid™, and molnupiravir. All in all, we underscore that theranostics as a concept and practice is essential for efficient and safe health interventions against COVID-19 and other ecological crises in the 21st century.

MXene-Based Nanomaterials for Biomedical Applications: Healthier Substitute Materials for the Future

MXene-based nanomaterial is a revolution 2D material achieving outstanding scientific attention owing to its universal characteristics for different applications (such as electronic appliances, power production, sensors, drug transfer, and biomedical). Although, the cytotoxic consequences of MXene have a considerable circumstance. Thus, rigorous investigation of the biocompatibility of MXene is a crucial prerequisite, formerly the preface to the human biological approach. Literature reveals functional outcomes wherever MXenes are used in vitro and in vivo cancer representatives. It affects drug transfer methods, sensoring electrodes, and assisting mechanisms for photothermal treatment and hyperthermy techniques. In this review, the synthesis process (such as top-down and bottom-up approaches) and properties (such as mechanical, electrical, optical, oxidative/thermal stability, and magnetic) of MXene-based nanomaterials (NMs) are discussed. In addition, the different applications (such as tissue engineering, cancer theranostic, and other biomedical [such as drug delivery biosensors and surface-enhanced Raman spectroscopy substrates for biomedical applications], antiviral, and immunomodulatory properties against SARS-CoV-2) of MXene-based NMs are discussed in detail. Finally, the conclusion, existing challenges, and future outlooks are highlighted for more scope in this field.

Biogenic Selenium Nanoparticles in Biomedical Sciences: Properties, Current Trends, Novel Opportunities and Emerging Challenges in Theranostic Nanomedicine.

Selenium is an important dietary supplement and an essential trace element incorporated into selenoproteins with growth-modulating properties and cytotoxic mechanisms of action. However, different compounds of selenium usually possess a narrow nutritional or therapeutic window with a low degree of absorption and delicate safety margins, depending on the dose and the chemical form in which they are provided to the organism. Hence, selenium nanoparticles (SeNPs) are emerging as a novel therapeutic and diagnostic platform with decreased toxicity and the capacity to enhance the biological properties of Se-based compounds. Consistent with the exciting possibilities offered by nanotechnology in the diagnosis, treatment, and prevention of diseases, SeNPs are useful tools in current biomedical research with exceptional benefits as potential therapeutics, with enhanced bioavailability, improved targeting, and effectiveness against oxidative stress and inflammation-mediated disorders. In view of the need for developing eco-friendly, inexpensive, simple, and high-throughput biomedical agents that can also ally with theranostic purposes and exhibit negligible side effects, biogenic SeNPs are receiving special attention. The present manuscript aims to be a reference in its kind by providing the readership with a thorough and comprehensive review that emphasizes the current, yet expanding, possibilities offered by biogenic SeNPs in the biomedical field and the promise they hold among selenium-derived products to, eventually, elicit future developments. First, the present review recalls the physiological importance of selenium as an oligo-element and introduces the unique biological, physicochemical, optoelectronic, and catalytic properties of Se nanomaterials. Then, it addresses the significance of nanosizing on pharmacological activity (pharmacokinetics and pharmacodynamics) and cellular interactions of SeNPs. Importantly, it discusses in detail the role of biosynthesized SeNPs as innovative theranostic agents for personalized nanomedicine-based therapies. Finally, this review explores the role of biogenic SeNPs in the ongoing context of the SARS-CoV-2 pandemic and presents key prospects in translational nanomedicine.

Emerging concerns of infectious diseases and drug delivery challenges

Emerging infectious diseases are the infections that could be newly appeared or have existed demographic area with rapidly increasing in some geographic range. Among various types of emerging infectious diseases like Ebola, chikungunya, tuberculosis, SARS, MERS, avian flu, swine flu, Zika, and so on, very recently we have witnessed the emergence of recently recognized coronavirus infection as Covid-19 pandemic caused by SARS-CoV-2, which rapidly spread around the world. Various emerging factors precipitating disease emergence include environmental, demographic, or ecological that increase the contact of people with unfamiliar microbial agents or their host or promote dissemination. Here in this chapter, we reviewed the various emerging considerations of infectious diseases including factors responsible for emerging and re-emerging infectious diseases as well as drug delivery challenges to treat infectious diseases and various strategies to deal with these challenges including nanotheranostics. Nanotheranostics are showing potential toward real-time understanding, diagnosis, and monitoring the response of the chemotherapy during treatment with reduced nontarget toxicity and enhanced safety level in the recent research studies. © 2022 Elsevier Inc. All rights reserved.

Multimodal Imaging and Phototherapy of Cancer and Bacterial Infection by Graphene and Related Nanocomposites.

The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.

Protease-Responsive Peptide-Conjugated Mitochondrial-Targeting AIEgens for Selective Imaging and Inhibition of SARS-CoV-2-Infected Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to human health and lacks an effective treatment. There is an urgent need for both real-time tracking and precise treatment of the SARS-CoV-2-infected cells to mitigate and ultimately prevent viral transmission. However, selective triggering and tracking of the therapeutic process in the infected cells remains challenging. Here, we report a main protease (Mpro)-responsive, mitochondrial-targeting, and modular-peptide-conjugated probe (PSGMR) for selective imaging and inhibition of SARS-CoV-2-infected cells via enzyme-instructed self-assembly and aggregation-induced emission (AIE) effect. The amphiphilic PSGMR was constructed with tunable structure and responsive efficiency and validated with recombinant proteins, cells transfected with Mpro plasmid or infected by SARS-CoV-2, and a Mpro inhibitor. By rational construction of AIE luminogen (AIEgen) with modular peptides and Mpro, we verified that the cleavage of PSGMR yielded gradual aggregation with bright fluorescence and enhanced cytotoxicity to induce mitochondrial interference of the infected cells. This strategy may have value for selective detection and treatment of SARS-CoV-2-infected cells.

It's Time to Shift the Paradigm: Translation and Clinical Application of Non-αvß3 Integrin Targeting Radiopharmaceuticals.

For almost the entire period of the last two decades, translational research in the area of integrin-targeting radiopharmaceuticals was strongly focused on the subtype αvß3, owing to its expression on endothelial cells and its well-established role as a biomarker for, and promoter of, angiogenesis. Despite a large number of translated tracers and clinical studies, a clinical value of αvß3-integrin imaging could not be defined yet. The focus of research has, thus, been moving slowly but steadily towards other integrin subtypes which are involved in a large variety of tumorigenic pathways. Peptidic and non-peptidic radioligands for the integrins α5ß1, αvß6, αvß8, α6ß1, α6ß4, α3ß1, α4ß1, and αMß2 were first synthesized and characterized preclinically. Some of these compounds, targeting the subtypes αvß6, αvß8, and α6ß1/ß4, were subsequently translated into humans during the last few years. αvß6-Integrin has arguably attracted most attention because it is expressed by some of the cancers with the worst prognosis (above all, pancreatic ductal adenocarcinoma), which substantiates a clinical need for the respective theranostic agents. The receptor furthermore represents a biomarker for malignancy and invasiveness of carcinomas, as well as for fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), and probably even for Sars-CoV-2 (COVID-19) related syndromes. Accordingly, the largest number of recent first-in-human applications has been reported for radiolabeled compounds targeting αvß6-integrin. The results indicate a substantial clinical value, which might lead to a paradigm change and trigger the replacement of αvß3 by αvß6 as the most popular integrin in theranostics.

Smart materials: rational design in biosystems via artificial intelligence.

Industry 4.0 encompasses a new industrial revolution in which advanced manufacturing systems are interconnected with information technologies. These sophisticated data-gathering technologies have led to a shift toward smarter manufacturing processes involving the use of smart materials (SMs). The properties of SMs make them highly attractive for numerous biomedical applications. The integration of artificial intelligence (AI) enables them to be effectively used in the design of novel biomedical platforms to overcome shortcomings in the current biotechnology industry. This review summarizes recent advances in AI-assisted SMs for different healthcare products. The current challenges and future perspectives of AI-supported smart biosystems are also discussed, particularly with the regard to their applications in drug design, biosensors, theranostics, and electronic skins.

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.

Activity-Based Probes for Proteases Pave the Way to Theranostic Applications.

Proteases are important enzymes in health and disease. Their activities are regulated at multiple levels. In fact, proteases are synthesized as inactive proenzymes (zymogens) that are activated by proteolytic removal of their pro-peptide sequence and can remain active or their activity can be attenuated by complex formation with specific endogenous inhibitors or by limited proteolysis or degradation. Consequently, quite often, only a fraction of the protease molecules is in the active/functional form, thus, the abundance of a protease is not always linearly proportional to the (patho)physiological function(s). Therefore, assays to determine the active forms of proteases are needed, not only in research but also in molecular diagnosis and therapy. Activity-based probes (ABPs) are chemical entities that bind covalently to the active enzyme/protease. ABPs carry a detection tag to enable localization and quantification of specific enzymatic/proteolytic activities with applications in molecular imaging and diagnosis. Moreover, ABPs act as suicide inhibitors of proteases, which can be exploited for delineation of the functional role(s) of a given protease in (patho) biological context and as potential therapeutics. In this sense, ABPs represent new theranostic agents. We outline recent developments pertaining to ABPs for proteases with potential therapeutic applications, with the aim to highlight their importance in theranostics.

Advances in magnetic resonance tomography

This chapter sets out the most promising modern directions of research in the field of magnetic resonance imaging. These include multinuclear studies aimed at the exploration of magnetic resonance (MR) image contrast induced by exogeneous (fluorine-19, hyperpolarized noble gases) and “built-in” (phosphorus-31, sodium-23) contrast agents for potential clinical benefits. The chapter covers electrodynamic elements of MR scanners that increase signal-to-noise ratio in low-field magnetic resonance imaging (MRI), hyperpolarization techniques that allow several orders of magnitude improved sensitivity in low-field MRI, as well as MRI methods to study dynamics of pharmaceuticals introduced into the body. Special attention is given to MRI methods based upon magnetization transfer aimed at the detection of myelination defects of axons in the brain and functional MRI characterizing brain dynamic response to external stimuli. © 2022 Elsevier Ltd All rights reserved.

Applications of electrospraying in biosensing, diagnostics, and beyond

Worldwide, diseases have rapidly grown as challenging problems that require the development and innovation of biosensing and diagnostic systems. In response to the current COVID-19 crisis, the needs for massive testing are being pushed harder than ever, urging scientists and engineers to search for diagnostic tools that can quickly and effectively detect and prevent the spread of the coronavirus. One technical candidate, electrospray (E-spray), appears to be promising for aiding these efforts mainly by its simple, flexible setup, environmentally friendly process, as well as low cost. Moreover, E-spray process enables activity retention of biomolecules and high-throughput productions of several functional and sensitive micro-/nanoscale structures that can significantly improve biosensor performance. Herein, we provide up-to-date developments of E-spray in biosensing and diagnostics, starting with a short introduction about E-spray and biosensor, followed by the uses of E-spray in biochips fabrications, in tailoring of biosensor surfaces, as well as in productions of sensory particles and other biosensing systems. Then, we discuss limitations, challenges of the technique, and eventually end this chapter with conclusion and outlook. © 2021 Elsevier Inc.

Emerging Biomedical and Industrial Applications of Nanoporous Materials

Nanoporous materials is a fast-growing subset of nanomaterials with unique intrinsic properties. The advances in fabrication and characterization techniques have enabled scientists to tailor the properties and design a wide range of application specific nanoporous materials. This chapter highlights the key technological advancements that nanoporous materials have achieved in the frontiers of biomedical engineering across analyses, diagnostics and therapeutics. It draws attention to progressive studies like the membrane based organ-on-a-chip (OOC) models of the blood brain barrier and human alveolar that contributed to the advancements in the drug development studies of neurological diseases and COVID-19 to neurochemical biosensing and artificial portable kidneys (Fan et al., ACS Nano 13:8374–8381, 2019;Wang et al., Biotechnol. Bioeng. 114:184–194, 2017;Zhang et al., Adv. Sci. 8:1–14, 2021;Zhou et al., Anal. Chem. 91:3645–3651, 2019). A brief account of the versatile industrial applications of nanoporous materials in chromatography, nanoreactors, energy storage and cutting-edge concepts like nanosized photonic data storage is also illustrated with representative cases. © 2022, Springer Nature Switzerland AG.

Photoactive "Bionic Virus" Robustly Elicits the Synergy Anticancer Activity of Immunophotodynamic Therapy.

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core-shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications.

Redefining the importance of polylactide-co-glycolide acid (PLGA) in drug delivery.

The limitations of non-biodegradable polymers have paved the way for biodegradable polymers in the pharmaceutical and biomedical sciences over the years. Poly (lactic-co-glycolic acid) (PLGA), also known as "Smart polymer", is one of the most successfully developed biodegradable polymers due to its favorable properties, such as biodegradability, biocompatibility, controllable drug release profile, and ability to alter surface with targeting agents for diagnosis and treatment. The release behavior of drugs from PLGA delivery devices is influenced by the physicochemical properties of PLGA. In this review, the current state of the art of PLGA, its synthesis, physicochemical properties, and degradation are discussed to enunciate the boundaries of future research in terms of its applicability with the optimized design in today's modern age. The fundamental objective of this review is to highlight the significance of PLGA as a polymer in the field of cancer, cardiovascular diseases, neurological disorders, dentistry, orthopedics, vaccine therapy, theranostics and lastly emerging epidemic diseases like COVID-19. Furthermore, the coverage of recent PLGA-based drug delivery systems including nanosystems, microsystems, scaffolds, hydrogels, etc. has been summarized. Overall, this review aims to disseminate the PLGA-driven revolution of the drug delivery arena in the pharmaceutical and biomedical industry and bridge the lacunae between material research, preclinical experimentation, and clinical reality.

Polyaminoacid Based Core@shell Nanocarriers of 5-Fluorouracil: Synthesis, Properties and Theranostics Application.

Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug's toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80-200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI).