Current Trends and Prospects for Application of Green Synthesized Metal Nanoparticles in Cancer and COVID-19 Therapies.

Cancer and COVID-19 have been deemed as world health concerns due to the millions of lives that they have claimed over the years. Extensive efforts have been made to develop sophisticated, site-specific, and safe strategies that can effectively diagnose, prevent, manage, and treat these diseases. These strategies involve the implementation of metal nanoparticles and metal oxides such as gold, silver, iron oxide, titanium oxide, zinc oxide, and copper oxide, formulated through nanotechnology as alternative anticancer or antiviral therapeutics or drug delivery systems. This review provides a perspective on metal nanoparticles and their potential application in cancer and COVID-19 treatments. The data of published studies were critically analysed to expose the potential therapeutic relevance of green synthesized metal nanoparticles in cancer and COVID-19. Although various research reports highlight the great potential of metal and metal oxide nanoparticles as alternative nanotherapeutics, issues of nanotoxicity, complex methods of preparation, biodegradability, and clearance are lingering challenges for the successful clinical application of the NPs. Thus, future innovations include fabricating metal nanoparticles with eco-friendly materials, tailor making them with optimal therapeutics for specific disease targeting, and in vitro and in vivo evaluation of safety, therapeutic efficiency, pharmacokinetics, and biodistribution.

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.

Photothermal therapy using gold nanoparticles and a long-pulsed 755-nm alexandrite laser to treat facial photoaging in Asian skin: A prospective clinical trial.

BACKGROUND AND OBJECTIVES: Transdermally delivered gold nanoparticles (AuNPs) irradiated with near-infrared laser energy can create a photothermal effect within the sebaceous glands (SGs). Photothermal therapy (PTT) can be used clinically to reverse photoaging in SG-rich areas of the skin. Improvements in wrinkles and enlarged pores in Asian skin were assessed following AuNP-mediated PTT with a long-pulsed 755-nm alexandrite laser. STUDY DESIGN/MATERIALS AND METHODS: A single-arm, prospective trial was designed. Twenty Korean patients underwent three gold PTT interventions performed 4 weeks apart at laser hair-removal settings without cooling. At Week 20, changes in the wrinkle index (WI) and pore index (PI), size, and count were calculated using three-dimensional camera analyses. Overall improvements in wrinkles and pores (0-4 scale) were assessed by blinded investigators using standardized photographic comparisons. The subjects scored their satisfaction (0-10 scale) and treatment discomfort (0-10 scale). Safety data were also collected. RESULTS: There were significant reductions in the WI (8.3%, p < 0.01), pore size (23.1%, p = 0.035), and PI (19.9%, p = 0.034) in the periorbital areas at week 20 compared with baseline. The mean reductions in the size (22.5%, p = 0.027), count (16.5%, p = 0.048), and index (22.4%, p = 0.023) of the cheek pores were also significant. Investigators reported average scores of 3.2 ± 0.6 for improved wrinkle appearance, and 3.1 ± 0.7 for improvement in visible pores. Participants were moderately satisfied with the overall results (7.6 ± 1.8). Subjects felt moderate discomfort during treatment (4.7 ± 2.6). No serious or persistent adverse events occurred. CONCLUSIONS: AuNP-mediated PTT showed noticeable efficacy and tolerability in treating wrinkles and pores in Asian skin over a 12 week-follow-up. Further studies with a longer follow-up are needed to confirm the reduction in SG activity at the parameters used.

Metal-Based Compounds in Antiviral Therapy.

In recent years, the study of metal complexes and metal-based nanomaterials has aroused particular interest, leading to the promotion of new effective systems for the abatement of various viral diseases. Starting from the analysis of chemical properties, this review focuses on the employment of metal-based nanoparticles as antiviral drugs and how this interaction leads to a substantial enhancement in antiviral activity. The use of metal-based antiviral drugs has also spread for the formulation of antiviral vaccines, thanks especially to the remarkable adjuvant activities of some of the metal complexes. In particular, the small size and inert nature of Au- and Ag-based nanoparticles have been exploited for the design of systems for antiviral drug delivery, leading to the development of specific and safe therapies that lead to a decrease in side effects.

The Fate of Intranasally Instilled Silver Nanoarchitectures.

The intranasal administration of drugs allows an effective and noninvasive therapeutic action on the respiratory tract. In an era of rapidly increasing antimicrobial resistance, new approaches to the treatment of communicable diseases, especially lung infections, are urgently needed. Metal nanoparticles are recognized as a potential last-line defense, but limited data on the biosafety and nano/biointeractions preclude their use. Here, we quantitatively and qualitatively assess the fate and the potential risks associated with the exposure to a silver nanomaterial model (i.e., silver ultrasmall-in-nano architectures, AgNAs) after a single dose instillation. Our results highlight that the biodistribution profile and the nano/biointeractions are critically influenced by both the design of the nanomaterial and the chemical nature of the metal. Overall, our data suggest that the instillation of rationally engineered nanomaterials might be exploited to develop future treatments for (non)communicable diseases of the respiratory tract.

Antiviral potential of nanoparticles for the treatment of Coronavirus infections.

BACKGROUND: On 31st December 2019 in Wuhan, China, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was acknowledged. This virus spread quickly throughout the world causing a global pandemic. The World Health Organization declared COVID-19 a pandemic disease on 11th March 2020. Since then, the whole world has come together and have developed several vaccines against this deadly virus. Similarly, several alternative searches for pandemic disease therapeutics are still ongoing. One of them has been identified as nanotechnology. It has demonstrated significant promise for detecting and inhibiting a variety of viruses, including coronaviruses. Several nanoparticles, including gold nanoparticles, silver nanoparticles, quantum dots, carbon dots, graphene oxide nanoparticles, and zinc oxide nanoparticles, have previously demonstrated remarkable antiviral activity against a diverse array of viruses. OBJECTIVE: This review aims to provide a basic and comprehensive overview of COVID-19's initial global outbreak and its mechanism of infiltration into human host cells, as well as the detailed mechanism and inhibitory effects of various nanoparticles against this virus. In addition to nanoparticles, this review focuses on the role of several antiviral drugs used against COVID-19 to date. CONCLUSION: COVID-19 has severely disrupted the social and economic lives of people all over the world. Due to a lack of adequate medical facilities, countries have struggled to maintain control of the situation. Neither a drug nor a vaccine has a 100% efficacy rate. As a result, nanotechnology may be a better therapeutic alternative for this pandemic disease.

Stimulus-responsive nanomaterials under physical regulation for biomedical applications.

Cancer is a growing threat to human beings. Traditional treatments for malignant tumors usually involve invasive means to healthy human tissues, such as surgical treatment and chemotherapy. In recent years the use of specific stimulus-responsive materials in combination with some non-contact, non-invasive stimuli can lead to better efficacy and has become an important area of research. It promises to develop personalized treatment systems for four types of physical stimuli: light, ultrasound, magnetic field, and temperature. Nanomaterials that are responsive to these stimuli can be used to enhance drug delivery, cancer treatment, and tissue engineering. This paper reviews the principles of the stimuli mentioned above, their effects on materials, and how they work with nanomaterials. For this aim, we focus on specific applications in controlled drug release, cancer therapy, tissue engineering, and virus detection, with particular reference to recent photothermal, photodynamic, sonodynamic, magnetothermal, radiation, and other types of therapies. It is instructive for the future development of stimulus-responsive nanomaterials for these aspects.

Spherical Neutralizing Aptamer Inhibits SARS-CoV-2 Infection and Suppresses Mutational Escape.

New neutralizing agents against SARS-CoV-2 and associated mutant strains are urgently needed for the treatment and prophylaxis of COVID-19. Herein, we develop a spherical cocktail neutralizing aptamer-gold nanoparticle (SNAP) to block the interaction between the receptor-binding domain (RBD) of SARS-CoV-2 and host ACE2. With the multivalent aptamer assembly as well as the steric hindrance effect of the gold scaffold, SNAP exhibits exceptional binding affinity against the RBD with a dissociation constant of 3.90 pM and potent neutralization against authentic SARS-CoV-2 with a half-maximal inhibitory concentration of 142.80 fM, about 2 or 3 orders of magnitude lower than that of the reported neutralizing aptamers and antibodies. More importantly, the synergetic blocking strategy of multivalent multisite binding and steric hindrance ensures broad neutralizing activity of SNAP, almost completely blocking the infection of three mutant pseudoviruses. Overall, the SNAP strategy provides a new direction for the development of antivirus agents against SARS-CoV-2 and other emerging coronaviruses.

Hard Nanomaterials in Time of Viral Pandemics.

The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.

Nanotheranostic Application of Fluorescent Protein-Gold Nanocluster Hybrid Materials: A Mini-review.

The gold nanoclusters (Au NCs) are a special kind of gold nanomaterial containing several gold atoms. Because of their small size and large surface area, Au NCs possess macroscopic quantum tunneling and dielectric domain effects. Furthermore, Au NCs fluorescent materials have longer luminous time and better photobleaching resistance compared with other fluorescent materials. The synthetic process of traditional Au NCs is complicated. Traditional Au NCs are prepared mainly by using polyamide amine type dendrites, and sixteen alkyl trimethylamine bromide or sulfhydryl small molecule as stabilizers. They are consequently synthesized by the reduction of strong reducing agents such as sodium borohydride. Notably, these materials are toxic and environmental-unfriendly. Therefore, there is an urgent need to develop more effective methods for synthesizing Au NCs via a green approach. On the other hand, the self-assembly of protein gold cluster-based materials, and their biomedical applications have become research hotspots in this field. We have been working on the synthesis, assembly and application of protein conjugated gold clusters for a long time. In this review, the synthesis and assembly of protein-gold nanoclusters and their usage in cell imaging and other medical research are discussed.

Silver, copper and copper oxide nanoparticles in the fight against human viruses: progress and perspectives.

The rapid development of nanomedicine has created a high demand for silver, copper and copper oxide nanoparticles. Due to their high reactivity and potent antimicrobial activity, silver and copper-based nanomaterials have been playing an important role in the search for new alternatives for the treatment of several issues of concern, such as pathologies caused by bacteria and viruses. Viral diseases are a significant and constant threat to public health. The most recent example is the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, the object of the present review is to highlight recent progress in the biomedical uses of these metal nanoparticles for the treatment and prevention of human viral infections. We discuss the antiviral activity of AgNPs and Cu-based NPs, including their actions against SARS-CoV-2. We also discuss the toxicity, biodistribution and excretion of AgNPs and CuNPs, along with their uses in medical devices or on inert surfaces to avoid viral dissemination by fomites. The challenges and limitations of the biomedical use of these nanoparticles are presented.

Synthesis and immunogenicity assessment of a gold nanoparticle conjugate for the delivery of a peptide from SARS-CoV-2.

The development of vaccines is a crucial response against the COVID-19 pandemic and innovative nanovaccines could increase the potential to address this remarkable challenge. In the present study a B cell epitope (S461-493) from the spike protein of SARS-CoV-2 was selected and its immunogenicity validated in sheep. This synthetic peptide was coupled to gold nanoparticles (AuNP) functionalized with SH-PEG-NH2 via glutaraldehyde-mediated coupling to obtain the AuNP-S461-493 candidate, which showed in s.c.-immunized mice a superior immunogenicity (IgG responses) when compared to soluble S461-493; and led to increased expression of relevant cytokines in splenocyte cultures. Interestingly, the response triggered by AuNP-S461-493 was similar in magnitude to that induced using a conventional strong adjuvant (Freund's adjuvant). This study provides a platform for the development of AuNP-based nanovaccines targeting specific SARS-CoV-2 epitopes.

Silver nanoparticles as a potential treatment against SARS-CoV-2: A review.

Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and, today, in SARS-CoV-2, an outbreak that has struck explosively and uncontrollably beginning in December 2019 and has claimed the lives of more than 1.9 M people worldwide as of January 2021. The development of vaccines has taken one year, which is why it is necessary to investigate whether some already-existing alternatives that have been successfully developed in recent years can mitigate the pandemic's advance. Silver nanoparticles (AgNPs) have proved effective in antiviral action. Thus, in this review, several in vitro and in vivo studies of the effect of AgNPs on viruses that cause respiratory diseases are analyzed and discussed to promote an understanding of the possible interaction of AgNPs with SARS-CoV-2. The study focuses on several in vivo toxicological studies of AgNPs and a dose extrapolation to humans to determine the chief avenue of exposure. It can be concluded that the use of AgNPs as a possible treatment for SARS-CoV-2 could be viable, based on comparing the virus' behavior to that of similar viruses in in vivo studies, and that the suggested route of administration in terms of least degree of adverse effects is inhalation. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Architectured Therapeutic and Diagnostic Nanoplatforms for Combating SARS-CoV-2: Role of Inorganic, Organic, and Radioactive Materials.

Although extensive research is being done to combat SARS-CoV-2, we are yet far away from a robust conclusion or strategy. With an increased amount of vaccine research, nanotechnology has found its way into vaccine technology. Researchers have explored the use of various nanostructures for delivering the vaccines for enhanced efficacy. Apart from acting as delivery platforms, multiple studies have shown the application of inorganic nanoparticles in suppressing the growth as well as transmission of the virus. The present review gives a detailed description of various inorganic nanomaterials which are being explored for combating SARS-CoV-2 along with their role in suppressing the transmission of the virus either through air or by contact with inanimate surfaces. The review further discusses the use of nanoparticles for development of an antiviral coating that may decrease adhesion of SARS-CoV-2. A separate section has been included describing the role of nanostructures in biosensing and diagnosis of SARS-CoV-2. The role of nanotechnology in providing an alternative therapeutic platform along with the role of radionuclides in SARS-CoV-2 has been described briefly. Based on ongoing research and commercialization of this nanoplatform for a viral disease, the nanomaterials show the potential in therapy, biosensing, and diagnosis of SARS-CoV-2.

Antiviral Activity of Nanomaterials against Coronaviruses.

One of the challenges facing by world nowadays is the generation of new pathogens that cause public health issues. Coronavirus (CoV) is one of the severe pathogens that possess the RNA (ribonucleic acid) envelop, and extensively infect humans, birds, and other mammals. The novel strain "SARS-CoV-2" (severe acute respiratory syndrome coronavirus-2) causes deadly infection all over the world and presents a pandemic situation nowadays. The SARS-CoV-2 has 40 different strains that create a worrying situation for health authorities. The virus develops serious pneumonia in infected persons and causes severe damage to the lungs. There is no vaccine available for this virus up to present. To cure this type of infections by making vaccines and antiviral drugs is still a major challenge for researchers. Nanotechnology covering a multidisciplinary field may find the solution to this lethal infection. The interaction of nanomaterials and microorganisms is considered as a potential treatment method because the nanomaterials owe unique physicochemical properties. The aim of this review is to present an overview of previous and recent studies of nanomaterials against coronaviruses and to provide possible new strategies for upcoming research using the nanotechnology platform.

A molecular docking study repurposes FDA approved iron oxide nanoparticles to treat and control COVID-19 infection.

COVID-19, is a disease resulting from the SARS-CoV-2 global pandemic. Due to the current global emergency and the length of time required to develop specific antiviral agent(s) and a vaccine for SARS-CoV-2, the world health organization (WHO) adopted the strategy of repurposing existing medications to treat COVID-19. Iron oxide nanoparticles (IONPs) were previously approved by the US food and drug administration (FDA) for anemia treatment and studies have also demonstrated its antiviral activity in vitro. Therefore, we performed a docking study to explore the interaction of IONPs (Fe2O3 and Fe3O4) with the spike protein receptor binding domain (S1-RBD) of SARS-CoV-2 that is required for virus attachment to the host cell receptors. A similar docking analysis was also performed with hepatitis C virus (HCV) glycoproteins E1 and E2. These studies revealed that both Fe2O3 and Fe3O4 interacted efficiently with the SARS-CoV-2 S1-RBD and to HCV glycoproteins, E1 and E2. Fe3O4 formed a more stable complex with S1-RBD whereas Fe2O3 favored HCV E1 and E2. These interactions of IONPs are expected to be associated with viral proteins conformational changes and hence, viral inactivation. Therefore, we recommend FDA-approved-IONPs to proceed for COVID-19 treatment clinical trials.