Ag Nanoparticles for Biomedical Applications—Synthesis and Characterization—A Review

Silver nanoparticles have been intensively studied over a long period of time because they exhibit antibacterial properties in infection treatments, wound healing, or drug delivery systems. The advantages that silver nanoparticles offer regarding the functionalization confer prolonged stability and make them suitable for biomedical applications. Apart from functionalization, silver nanoparticles exhibit various shapes and sizes depending on the conditions used through their fabrications and depending on their final purpose. This paper presents a review of silver nanoparticles with respect to synthesis procedures, including the polluting green synthesis. Currently, the most commonly used characterization techniques required for nanoparticles investigation in antibacterial treatments are described briefly, since silver nanoparticles possess differences in their structure or morphology.     

‘All That Glitters Is Not Gold’: High-Resolution Crystal Structures of Ligand-Protein Complexes Need Not Always Represent Confident Binding Poses

Our understanding of the structure–function relationships of biomolecules and thereby applying it to drug discovery programs are substantially dependent on the availability of the structural information of ligand–protein complexes. However, the correct interpretation of the electron density of a small molecule bound to a crystal structure of a macromolecule is not trivial. Our analysis involving quality assessment of ~0.28 million small molecule–protein binding site pairs derived from crystal structures corresponding to ~66,000 PDB entries indicates that the majority (65%) of the pairs might need little (54%) or no (11%) attention. Out of the remaining 35% of pairs that need attention, 11% of the pairs (including structures with high/moderate resolution) pose serious concerns. Unfortunately, most users of crystal structures lack the training to evaluate the quality of a crystal structure against its experimental data and, in general, rely on the resolution as a ‘gold standard’ quality metric. Our work aims to sensitize the non-crystallographers that resolution, which is a global quality metric, need not be an accurate indicator of local structural quality. In this article, we demonstrate the use of several freely available tools that quantify local structural quality and are easy to use from a non-crystallographer’s perspective. We further propose a few solutions for consideration by the scientific community to promote quality research in structural biology and applied areas.     

Antifungal Effect of Nanoparticles against COVID-19 Linked Black Fungus: A Perspective on Biomedical Applications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that has caused a ‘coronavirus disease 2019’ (COVID-19) pandemic in multiple waves, which threatens human health and public safety. During this pandemic, some patients with COVID-19 acquired secondary infections, such as mucormycosis, also known as black fungus disease. Mucormycosis is a serious, acute, and deadly fungal infection caused by Mucorales-related fungal species, and it spreads rapidly. Hence, prompt diagnosis and treatment are necessary to avoid high mortality and morbidity rates. Major risk factors for this disease include uncontrolled diabetes mellitus and immunosuppression that can also facilitate increases in mucormycosis infections. The extensive use of steroids to prevent the worsening of COVID-19 can lead to black fungus infection. Generally, antifungal agents dedicated to medical applications must be biocompatible, non-toxic, easily soluble, efficient, and hypoallergenic. They should also provide long-term protection against fungal growth. COVID-19-related black fungus infection causes a severe increase in fatalities. Therefore, there is a strong need for the development of novel and efficient antimicrobial agents. Recently, nanoparticle-containing products available in the market have been used as antimicrobial agents to prevent bacterial growth, but little is known about their efficacy with respect to preventing fungal growth, especially black fungus. The present review focuses on the effect of various types of metal nanoparticles, specifically those containing silver, zinc oxide, gold, copper, titanium, magnetic, iron, and carbon, on the growth of various types of fungi. We particularly focused on how these nanoparticles can impact the growth of black fungus. We also discussed black fungus co-infection in the context of the global COVID-19 outbreak, and management and guidelines to help control COVID-19-associated black fungus infection. Finally, this review aimed to elucidate the relationship between COVID-19 and mucormycosis.     

A Mild,Highly Efficient Addition of Alkynes to Aldehydes Catalyzed by Titanium Dioxide‐Supported Silver Nanoparticles

Titanium dioxide‐supported silver nanoparticles were utilized as a highly efficient catalyst for the addition of terminal alkynes to aldehydes to prepare propargylic alcohols with the promotion by triphenylphosphine. Both a significant support effect and a ligand effect were observed in the catalytic reaction. With this protocol, various propargylic alcohol derivatives were synthesized from aldehydes and terminal alkynes in good to excellent yields. Furthermore, the catalyst could be recovered and reused effectively without obvious reduction in catalytic activity.     

Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids

Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. The level of exposure to nanosilver is constantly raising, and a growing body of research highlights that it is harmful to the health, especially the nervous system, of humans. The potential pathways through which nanosilver affects neurons include the release of silver ions and the associated induction of oxidative stress. To better understand the mechanisms underlying the neurotoxicity of nanosilver, in this study we exposed male Wistar rats to 0.5 mg/kg body weight of AgNPs coated with bovine serum albumin (BSA), polyethylene glycol (PEG), or citrate, or to AgNO₃ as a source of silver ions for 28 days and assessed the expression of antioxidant defense markers in the hippocampus of the exposed animals after 1 week of spatial memory training. We also evaluated the influence of AgNPs coating on neurosteroidogenesis in the rat hippocampus. The results showed that AgNPs disrupted the antioxidant system in the hippocampus and induced oxidative stress in a coating-dependent manner, which could potentially be responsible for neurodegeneration and cognitive disorders. The analysis of the influence of AgNPs on neurosteroids also indicated coating-dependent modulation of steroid levels with a significant decrease in the concentrations of progesterone and 17α-progesterone in AgNPs(BSA), AgNPs(PEG), and Ag⁺ groups. Furthermore, exposure to AgNPs or Ag⁺ resulted in the downregulation of selected genes involved in antioxidant defense (Cat), neurosteroid synthesis (Star, Hsd3b3, Hsd17b1, and Hsd17b10), and steroid metabolism (Ar, Er1, and Er2). In conclusion, depending on the coating material used for their stabilization, AgNPs induced oxidative stress and modulated the concentrations of steroids as well as the expression of genes involved in steroid synthesis and metabolism.     

Facile Deposition of Silver Nanoparticles on Photonic Cellulose Nanocrystals Films: A Study on Solvent Stability and Post Antibacterial Activity

Cellulose nanocrystals (CNCs) incorporated with silver nanoparticles (AgNPs) photonic films have drawn considerable attention due to their plasmonic chiroptical activity. However, the exploitation of some fundamental properties for practical use such as the affinity analysis of metal nanoparticles attached to the surface of photonic films according to the solvent compatibility and antibacterial activity under physical conditions has yet not been studied. Hence, a facile process of in situ deposition of AgNPs into the chiral structure of CNC films is proposed. CNC photonic films, cross-linked by glutaraldehyde are prepared. This interaction generated the solvents-stable photonic film with a considerable amount of unreacted aldehyde functional groups that facilitates the reduction of Ag salt to AgNPs. The formed AgNPs in the photonic films show excellent stability over immersion in various polar and non-polar solvents. The post-solvent treated photonic films display excellent contact-based antibacterial behavior against gram-negative Escherichia coli.     

Silver Nanoparticles Impair Cognitive Functions and Modify the Hippocampal Level of Neurotransmitters in a Coating-Dependent Manner

Due to their potent antibacterial properties, silver nanoparticles (AgNPs) are widely used in industry and medicine. However, they can cross the brain–blood barrier, posing a risk to the brain and its functions. In our previous study, we demonstrated that oral administration of bovine serum albumin (BSA)-coated AgNPs caused an impairment in spatial memory in a dose-independent manner. In this study, we evaluated the effects of AgNPs coating material on cognition, spatial memory functioning, and neurotransmitter levels in rat hippocampus. AgNPs coated with BSA (AgNPs(BSA)), polyethylene glycol (AgNPs(PEG)), or citrate (AgNPs(Cit)) or silver ions (Ag⁺) were orally administered at a dose of 0.5 mg/kg b.w. to male Wistar rats for a period of 28 days, while the control (Ctrl) rats received 0.2 mL of water. The acquisition and maintenance of spatial memory related to place avoidance were assessed using the active allothetic place avoidance task, in which rats from AgNPs(BSA), AgNPs(PEG), and Ag⁺ groups performed worse than the Ctrl rats. In the retrieval test assessing long-term memory, only rats from AgNPs(Cit) and Ctrl groups showed memory maintenance. The analysis of neurotransmitter levels indicated that the ratio between serotonin and dopamine concentration was disturbed in the AgNPs(BSA) rats. Furthermore, treatment with AgNPs or Ag⁺ resulted in the induction of peripheral inflammation, which was reflected by the alterations in the levels of serum inflammatory mediators. In conclusion, depending on the coating material used for their stabilization, AgNPs induced changes in memory functioning and concentration of neurotransmitters.     

Combinatory Effects of Cerium Dioxide Nanoparticles and Acetaminophen on the Liver—A Case Study of Low-Dose Interactions in Human HuH-7 Cells

The interactions between pharmaceuticals and nanomaterials and its potentially resulting toxicological effects in living systems are only insufficiently investigated. In this study, two model compounds, acetaminophen, a pharmaceutical, and cerium dioxide, a manufactured nanomaterial, were investigated in combination and individually. Upon inhalation, cerium dioxide nanomaterials were shown to systemically translocate into other organs, such as the liver. Therefore we picked the human liver cell line HuH-7 cells as an in vitro system to investigate liver toxicity. Possible synergistic or antagonistic metabolic changes after co-exposure scenarios were investigated. Toxicological data of the water soluble tetrazolium (WST-1) assay for cell proliferation and genotoxicity assessment using the Comet assay were combined with an untargeted as well as a targeted lipidomics approach. We found an attenuated cytotoxicity and an altered metabolic profile in co-exposure experiments with cerium dioxide, indicating an interaction of both compounds at these endpoints. Single exposure against cerium dioxide showed a genotoxic effect in the Comet assay. Conversely, acetaminophen exhibited no genotoxic effect. Comet assay data do not indicate an enhancement of genotoxicity after co-exposure. The results obtained in this study highlight the advantage of investigating co-exposure scenarios, especially for bioactive substances.     

Modulatory Effects of Biosynthesized Gold Nanoparticles Conjugated with Curcumin and Paclitaxel on Tumorigenesis and Metastatic Pathways—In Vitro and In Vivo Studies

Background: Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life. Methods: The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin–Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP–Curcumin (Au-C), AuNP–Paclitaxel (Au-P), and AuNP–Curcumin–Paclitaxel (Au-CP)) in various in vitro and in vivo models. Results: The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups. Conclusions: Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses.     

Modification of TiAlV Alloys with Hybrid Layers Containing Metallic Nanoparticles Obtained by the Sol–Gel Method: Surface and Structural Properties

The aim of the work was to obtain hybrid coatings containing silver, copper, and zinc nanoparticles on the TiAlV medical alloy via a sol–gel process. The developed layers were designed to bring about a bactericidal and fungicidal effect, as well as for protection against surgical scratches during the implantation of implants used in veterinary medicine. In this work, the authors focused on evaluating the microstructure (SEM + EDS); the structure (XRD, FTIR); and the surface properties, such as wettability, free surface energy, and roughness of layers with various concentrations of metallic nanoparticles (2 and 5 mol %). Our results confirmed that the sol–gel method enables the easy manufacturing of hybrid layers endowed with different porosity values as well as various shapes and sizes of metallic nanoparticles. A higher concentration of nanoparticles was observed on the surface containing 5 mol % of metallic salts. The highest degree of homogeneity was obtained for the layers containing silver nanoparticles. In addition, the silver nanoparticles were round and had the smallest dimensions, even below 20 nm. The FTIR and XRD structural studies confirmed the presence of an organosilicon matrix containing all three types of the metallic particles. We conclude that the higher concentration of nanoparticles influenced the alloy surface parameters.     

Controlled Reversible Anchoring of η6‐Arene/TsDPEN‐ Ruthenium(II) Complex onto Magnetic Nanoparticles: A New Strategy for Catalyst Separation and Recycling

A new catalyst separation and recycling protocol combining magnetic nanoparticles and host‐guest assembly was developed. The catalyst, (η⁶‐arene)[N‐(para‐toluenesulfonyl)‐1,2‐diphenylethylenediamine]ruthenium trifluoromethanesulfonate [Ru(OTf)(TsDPEN)(η⁶‐arene)] bearing a dialkylammonium salt tag, was easily separated from the reaction mixtures by magnet‐assisted decantation, on basis of the formation of a pseudorotaxane complex by using dibenzo[24]crown‐8‐modified Fe₃O₄ nanoparticles. The ruthenium catalyst has been successfully reused at least 5 times with the retention of enantioselectivity but at the expense of relatively low catalytic activities in the asymmetric hydrogenation of 2‐methylquinoline.