Multifunctional integration of tungsten oxide (WO3) coating: A versatile approach for enhanced performance of antibiotics against single mixed bacterial infections.

Nanomaterials containing tungsten (TNMs), characterized by diverse nanostructures had been extensively used in biomedical sector. Despite numerous reports focusing on TNM applications in specific biomedical areas, there is a noticeable absence of comprehensive studies that focused on detailed characterization of nanomaterials along with their biological applications. The present work described the structural, morphological, and antimicrobial properties of tungsten oxide (WO3) nanoparticles coated by antibiotics (nanobiotics), and their application on single and mixed bacterial culture. The nanobiotics included in this study were WO3 coated with ampicillin (W+A), WO3 coated with penicillin (P+W), and WO3 coated with ciprofloxacin (C+W). Techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray spectroscopy (EDX), Fourier transforms infrared spectroscopy (FTIR), Rrman spectroscopy, and UV-visible spectroscopy were used to characterize synthesized nanoparticles. The minimum inhibitory concentration of C+W nanobiotic against S. aureus, E. coli, and mixed culture (S. aureus +E. coli) was lower than that of P+W and A+W. The impact of incubation period showed significant differences for each of nanobiotic against S. aureus, E. coli, and mixed culture. However, there were also non-significant differences among incubation periods for antibacterial activity of nanobiotics. It was pertinent to note that percentage variation in susceptibility of S. aureus with respect to mixed culture remained higher as compared to E. coli, indicating it stronger candidate imposing resistance. This paper thus suggested the strategy of coating of antibiotics with with WO3 nanoparticles as an ideal combination for resistance modulation against single and mixed culture bacteria.

Antimicrobial Activity of Biogenic Metal Oxide Nanoparticles and Their Synergistic Effect on Clinical Pathogens.

The rising prevalence of antibiotic-resistance is currently a grave issue; hence, novel antimicrobial agents are being explored and developed to address infections resulting from multiple drug-resistant pathogens. Biogenic CuO, ZnO, and WO3 nanoparticles can be considered as such agents. Clinical isolates of E. coli, S. aureus, methicillin-resistant S. aureus (MRSA), and Candida albicans from oral and vaginal samples were treated with single and combination metal nanoparticles incubated under dark and light conditions to understand the synergistic effect of the nanoparticles and their photocatalytic antimicrobial activity. Biogenic CuO and ZnO nanoparticles exhibited significant antimicrobial effects under dark incubation which did not alter on photoactivation. However, photoactivated WO3 nanoparticles significantly reduced the number of viable cells by 75% for all the test organisms, thus proving to be a promising antimicrobial agent. Combinations of CuO, ZnO, and WO3 nanoparticles demonstrated synergistic action as a significant increase in their antimicrobial property (>90%) was observed compared to the action of single elemental nanoparticles. The mechanism of the antimicrobial action of metal nanoparticles both in combination and in isolation was assessed with respect to lipid peroxidation due to ROS (reactive oxygen species) generation by measuring malondialdehyde (MDA) production, and the damage to cell integrity using live/dead staining and quantitating with the use of flow cytometry and fluorescence microscopy.

Aluminum-Substituted Keggin Germanotungstate [HAl(H2O)GeW11O39]4-: Synthesis, Characterization, and Antibacterial Activity.

We report on the new monosubstituted aluminum Keggin-type germanotungstate (C4H12N)4[HAlGeW11O39(H2O)]·11H2O ([Al(H2O)GeW11]4-), which has been synthesized at room temperature via rearrangement of the dilacunary [γ-GeW10O36]8- polyoxometalate precursor. [Al(H2O)GeW11]4- has been characterized thoroughly both in the solid state by single-crystal and powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and elemental analysis as well as in solution by cyclic voltammetry (CV) 183W, 27Al NMR and UV-vis spectroscopy. A study on the antibacterial properties of [Al(H2O)GeW11]4- and the known aluminum(III)-centered Keggin polyoxotungstates (Al-POTs) α-Na5[AlW12O40] (α-[AlW12O40]5-) and Na6[Al(AlOH2)W11O39] ([Al(AlOH2)W11O39]6-) revealed enhanced activity for all three Al-POTs against the Gram-negative bacterium Moraxella catarrhalis (minimum inhibitory concentration (MIC) up to 4 µg mL-1) and the Gram-positive Enterococcus faecalis (MIC up to 128 µg mL-1) compared to the inactive Al(NO3)3 salt (MIC > 256 µg mL-1). CV indicates the redox activity of the Al-POTs as a dominating factor for the observed antibacterial activity with increased tendency to reduction, resulting in increased antibacterial activity of the POT.

Selective Synthesis of α-, ß-, and γ-Ag2WO4 Polymorphs: Promising Platforms for Photocatalytic and Antibacterial Materials.

Silver tungstate (Ag2WO4) shows structural polymorphism with different crystalline phases, namely, orthorhombic, hexagonal, and cubic structures that are commonly known as α, ß, and γ, respectively. In this work, these Ag2WO4 polymorphs were selectively and successfully synthesized through a simple precipitation route at ambient temperature. The polymorph-controlled synthesis was conducted by means of the volumetric ratios of the silver nitrate/tungstate sodium dehydrate precursors in solution. The structural and electronic properties of the as-synthesized Ag2WO4 polymorphs were investigated by using a combination of X-ray diffraction and Rietveld refinements, X-ray absorption spectroscopy, X-ray absorption near-edge structure spectroscopy, field-emission scanning electron microscopy images, and photoluminescence. To complement and rationalize the experimental results, first-principles calculations, at the density functional theory level, were carried out, leading to an unprecedented glimpse into the atomic-level properties of the morphology and the exposed surfaces of Ag2WO4 polymorphs. Following the analysis of the local coordination of Ag and W cations (clusters) at each exposed surface of the three polymorphs, the structure-property relationship between the morphology and the photocatalytic and antibacterial activities against amiloride degradation under ultraviolet light irradiation and methicillin-resistant Staphylococcus aureus, respectively, was investigated. A possible mechanism of the photocatalytic and antibacterial activity as well the formation process and growth of the polymorphs is also explored and proposed.

Multicomponent Self-Assembly of a Giant Heterometallic Polyoxotungstate Supercluster with Antitumor Activity.

The hierarchical aggregation of molecular nanostructures from multiple components is a grand synthetic challenge, which requires highly selective linkage control. We demonstrate how two orthogonal linkage groups, that is, organotin and lanthanide cations, can be used to drive the aggregation of a giant molecular metal oxide superstructure. The title compound {[(Sn(CH3 )2 )2 O]4 {[CeW5 O18 ] [TeW4 O16 ][CeSn(CH3 )2 ]4 [TeW8 O31 ]4 }2 }46- (1 a) features dimensions of ca. 2.2×2.3×3.4 nm3 and a molecular weight of ca. 25 kDa. Structural analysis shows the hierarchical aggregation from several independent subunits. Initial biomedical tests show that 1 features an inhibitory effect on the proliferation of HeLa cells based on an apoptosis pathway. In vivo experiments in mice reveal the antiproliferative activity of 1 and open new paths for further development of this new compound class.

Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW8 O30 } Determined by Single-Cell Proteomics Analysis.

The 10-nuclear heteroatom cluster modified {SbW8 O30 } was successfully synthesized and exhibited inhibitory activity (IC50 =0.29 µM). Based on proteomics analysis, Na4 Ni2 Sb2 W2 -SbW8 inhibited ATP production by affecting the expression of 16 related proteins, hindering metabolic functions in vivo and cell proliferation due to reactive oxygen species (ROS) stress. In particular, the low expression of FAD/FMN-binding redox enzymes (relative expression ratio of the experimental group to the control=0.43843) could be attributed to the redox mechanism of Na4 Ni2 Sb2 W2 -SbW8 , which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATP formation. An electrochemical study showed that Na4 Ni2 Sb2 W2 -SbW8 combined with FMN to form Na4 Ni2 Sb2 W2 -SbW8 -2FMN complex through a one-electron process of the W atoms. Na4 Ni2 Sb2 W2 -SbW8 acted as catalase and glutathione peroxidase to protect the cell from ROS stress, and the inhibition rates were 63.3 % at 1.77 µM of NADPH and 86.06 % at 10.62 µM of 2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.

Tetra-(p-tolyl)antimony(III)-Containing Heteropolytungstates, [{(p-tolyl)SbIII}4(A-α-XW9O34)2]n- (X = P, As, or Ge): Synthesis, Structure, and Study of Antibacterial and Antitumor Activity.

We have synthesized and structurally characterized three tetra-(p-tolyl)antimony(III)-containing heteropolytungstates, [{(p-tolyl)SbIII}4(A-α-XW9O34)2]n- [X = PV (1-P), AsV (1-As), or GeIV (1-Ge)], in aqueous solution using conventional, one-pot procedures. The polyanions 1-P, 1-As, and 1-Ge were fully characterized in the solid state and in solution and were shown to be soluble and stable in aqueous medium at pH 7. Biological studies demonstrated that all three polyanions possess significant antibacterial and antitumor activities. The minimum inhibitory concentrations of 1-P, 1-As, and 1-Ge were determined against four kinds of bacteria, including the two pathogenic bacteria strains, Vibrio parahaemolyticus and Vibrio vulnificus. The three novel polyanions also showed high cytotoxic potency in the human cell lines A549 (non-small cell lung cancer), CH1/PA-1 (ovarian teratocarcinoma), and SW480 (colon carcinoma).

Robust Antibacterial Activity of Tungsten Oxide (WO3-x) Nanodots.

Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-x), synthesized by a simple one-pot synthetic approach, were found to exhibit strong antibacterial capabilities. The analyses with colony-forming units (CFU) showed an excellent antibacterial activity of WO3-x against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damages to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase the germicidal activity of WO3-x nanodots, a 30 min exposure to sunlight combined with 50 µg/mL WO3-x nanodots showed a 70% decrease in E. coli viability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. The cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-x nanodots on eukaryotic cells, which demonstrated their general biocompatibility. In summary, our results suggest WO3-x nanodots have considerable potential in antibacterial applications, while also being biocompatible at large.

Polyoxometalates as Potential Next-Generation Metallodrugs in the Combat Against Cancer.

Polyoxometalates (POMs) are an emerging class of inorganic metal oxides, which over the last decades demonstrated promising biological activities by the virtue of their great diversity in structures and properties. They possess high potential for the inhibition of various tumor types; however, their unspecific interactions with biomolecules and toxicity impede their clinical usage. The current focus of the field of biologically active POMs lies on organically functionalized and POM-based nanocomposite structures as these hybrids show enhanced anticancer activity and significantly reduced toxicity towards normal cells in comparison to unmodified POMs. Although the antitumor activity of POMs is well documented, their mechanisms of action are still not well understood. In this Review, an overview is given of the cytotoxic effects of POMs with a special focus on POM-based hybrid and nanocomposite structures. Furthermore, we aim to provide proposed mode of actions and to identify molecular targets. POMs are expected to develop into the next generation of anticancer drugs that selectively target cancer cells while sparing healthy cells.

From Photoinduced to Dark Cytotoxicity through an Octahedral Cluster Hydrolysis.

Octahedral molybdenum and tungsten clusters have potential biological applications in photodynamic therapy and bioimaging. However, poor solubility and hydrolysis stability of these compounds hinder their application. The first water-soluble photoluminescent octahedral tungsten cluster [{W6 I8 }(DMSO)6 ](NO3 )4 was synthesised and demonstrated to be at least one order of magnitude more stable towards hydrolysis than its molybdenum analogue. Biological studies of the compound on larynx carcinoma cells suggest that it has a significant photoinduced toxicity, while the dark toxicity increases with the increase of the degree of hydrolysis. The increase of the dark toxicity is associated with the in situ generation of nanoparticles that clog up the cisternae of rough endoplasmic reticulum.

WO3/Pt nanoparticles promote light-induced lipid peroxidation and lysosomal instability within tumor cells.

Although metal-metal oxide nanoparticles have attracted considerable interest as catalysts, they have attracted little interest in nanomedicine. This is likely due to the fact that metal oxide semiconductors generally require biologically harmful ultraviolet excitation. In contrast, this study focuses upon WO3/Pt nanoparticles, which can be excited by visible light. To optimize the nanoparticles' catalytic performance, platinization was performed at alkaline pH. These nanoparticles destroyed organic dyes, consumed dissolved oxygen and produced hydroxyl radicals. 4T1 breast cancer cells internalized WO3/Pt nanoparticles within the membrane-bound endo-lysosomal compartment as shown by electron and fluorescence microscopy. During visible light exposure, but not in darkness, WO3/Pt nanoparticles manufacture reactive oxygen species, promote lipid peroxidation, and trigger lysosomal membrane disruption. As cells of the immune system degrade organic molecules, produce reactive oxygen species, and activate the lipid peroxidation pathway within target cells, these nanoparticles mimic the chemical attributes of immune effector cells. These biomimetic nanoparticles should become useful in managing certain cancers, especially ocular cancer.

WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo.

To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO3/Pt nanoparticles that mimic a leukocyte's functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO3/Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye's anterior chamber, we show that WO3/Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer.

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0.15%) or allopurinol (30 µg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H2O2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H2O2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H2O2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production.

[Murine peritoneal neutrophil activation upon tungsten nanoparticles exposure in vivo].

Two examples of tungsten carbide nanoparticles (d = 15 nm, 50 nm) and tungsten carbide nanoparticles with 8% cobalt (d = 50 nm) have been found to induce the neutrophil activation 3 h and 36 h after intraperitoneal administration in the doses 0.005; 0.025; 0.05; 0.25; 0.5; 1; 2.5 and 5 microgram per 1 gram body weight to FVB mice. Neutrophil activation was calculated based on the CD11b and S100 antigen expression. Effect of nanoparticles is bimodal for all tested examples.

2D Nanozymes Modulate Gut Microbiota and T-Cell Differentiation for Inflammatory Bowel Disease Management.

Intestinal commensal microbiota dysbiosis and immune dysfunction are significant exacerbating factors in inflammatory bowel disease (IBD). To address these problems, Pluronic F-127-coated tungsten diselenide (WSe2 @F127) nanozymes are developed by simple liquid-phase exfoliation. The abundant valence transitions of elemental selenium (Se2- /Se4+ ) and tungsten (W4+ /W6+ ) enable the obtained WSe2 @F127 nanozymes to eliminate reactive oxygen/nitrogen species. In addition, the released tungsten ions are capable of inhibiting the proliferation of Escherichia coli. In a model of dextran sodium sulfate-induced colitis, WSe2 @F127 nanozymes modulate the gut microbiota by increasing the abundance of bacteria S24-7 and significantly reducing the abundance of Enterobacteriaceae. Moreover, WSe2 @F127 nanozymes inhibit T-cell differentiation and improve intestinal immune barrier function in a model of Crohn's disease. The WSe2 @F127 nanozymes effectively alleviate IBD by reducing oxidative stress damage, modulating intestinal microbial populations, and remodeling the immune barrier.

Indoor-Light-Activated Blue TiO2-Molecule-WO3 Visible Photocatalyst for Antibacterial Performance against Escherichia coli.

Currently used visible light catalysts either operate with high-power light sources or require prolonged periods of time for catalytic reactions. This presents a limitation regarding facile application in indoor environments and spaces frequented by the public. Furthermore, this gives rise to elevated power consumption. Here, we enhance photocatalytic performance with blue TiO2 and WO3 complexes covalently coupled through an organic molecule, 3-mercaptopropionic acid, under indoor light. Antibacterial experiments against 108 CFU/mL Escherichia coli (E. coli) suspensions were conducted under indoor light exposure conditions. They showed a sterilization effect of almost 90% within 70 min and nearly 100% after 110 min. The complex generates reactive oxygen species (ROS), such as •OH and O2•-, under natural air conditions. We also showed that h+ and •OH are important for sterilizing E. coli using common scavengers. This research highlights the potential of these complexes to generate ROS, effectively playing a crucial role in antibacterial effects under indoor light.

Effect of W-TiO2 composite to control microbiologically influenced corrosion on galvanized steel.

Microorganisms tend to colonize on solid metal/alloy surface in natural environment leading to loss of utility. Microbiologically influenced corrosion or biocorrosion usually increases the corrosion rate of steel articles due to the presence of bacteria that accelerates the anodic and/or cathodic corrosion reaction rate without any significant change in the corrosion mechanism. An attempt was made in the present study to protect hot-dip galvanized steel from such attack of biocorrosion by means of chemically modifying the zinc coating. W-TiO2 composite was synthesized and incorporated into the zinc bath during the hot-dipping process. The surface morphology and elemental composition of the hot-dip galvanized coupons were analyzed by scanning electron microscopy and energy dispersive X-ray spectroscopy. The antifouling characteristics of the coatings were analyzed in three different solutions including distilled water, seawater, and seawater containing biofilm scrapings under immersed conditions. Apart from electrochemical studies, the biocidal effect of the composite was evaluated by analyzing the extent of bacterial growth due to the presence and absence of the composite based on the analysis of total extracellular polymeric substance and total biomass using microtiter plate assay. The biofilm-forming bacteria formed on the surface of the coatings was cultured on Zobell Marine Agar plates and studied. The composite was found to be effective in controlling the growth of bacteria and formation of biofilm thereafter.

Natural Targeting Potent ROS-Eliminating Tungsten-Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease of pulmonary artery stenosis and blockage caused by abnormal pulmonary artery smooth muscle cells (PASMCs), with high morbidity and mortality. High levels of reactive oxygen species (ROS) in pulmonary arteries play a crucial role in inducing phenotypic switch and abnormal proliferation of PASMCs. However, antioxidants are rarely approved for the treatment of PH because of a lack of targeting and low bioavailability. In this study, the presence of an enhanced permeability and retention effect (EPR)-like effect in the pulmonary arteries of PH is revealed by tissue transmission electron microscopy (TEM). Subsequently, for the first time, tungsten-based polyoxometalate nanodots (WNDs) are developed with potent elimination of multiple ROS for efficient treatment of PH thanks to the high proportion of reduced W5+ . WNDs are effectively enriched in the pulmonary artery by intravenous injection because of the EPR-like effect of PH, and significantly prevent the abnormal proliferation of PASMCs, greatly improve the remodeling of pulmonary arteries, and ultimately improve right heart function. In conclusion, this work provides a novel and effective solution to the dilemma of targeting ROS for the treatment of PH.

Genotoxicity in the absence of inflammation after tungsten inhalation in mice.

Tungsten is used in several applications and human exposure may occur. To assess its pulmonary toxicity, we exposed male mice to nose-only inhalation of tungsten particles at 9, 23 or 132 mg/m3 (Low, Mid and High exposure) (45 min/day, 5 days/week for 2 weeks). Increased genotoxicity (assessed by comet assay) was seen in bronchoalveolar (BAL) fluid cells at Low and High exposure. We measured acellular ROS production, and cannot exclude that ROS contributed to the observed genotoxicity. We saw no effects on body weight gain, pulmonary inflammation, lactate dehydrogenase or protein in BAL fluid, pathology of liver or kidney, or on sperm counts. In conclusion, tungsten showed non-dose dependent genotoxicity in the absence of inflammation and therefore interpreted to be primary genotoxicity. Based on genotoxicity, a Lowest Observed Adverse Effect Concentration (LOAEC) could be set at 9 mg/m3. It was not possible to establish a No Adverse Effect Concentration (NOAEC).

New composition of tungsten has a broad range of antiviral activity.

The water-based combination of two inorganic chemical compounds such as sodium tungstate dihydrate-Na2WO4 × 2H2O and Aluminum sulfate octadecahydrate-Al2 (SO4) 3 × 18H2O that we have conditionally named 'Vomifal' has a broad antiviral activity in various DNA and RNA viruses, including Human Herpes Virus (HHV), African Swine Fever Virus (ASFV), Vaccinia Virus (VV), Hepatitis C Virus (HCV), Foot and Mouth Disease Virus (FMDV), Influenza A virus (A/Aichi/2/68 (H3N2)). In vitro and In vivo assays in several tissue cultures as well as in laboratory animals, conformed 'Vomifal' has a very low toxicity and the antiviral properties partially are due to its ability to induce gamma-IFN. Based on the results obtained, we can assume the presence of at least two mechanisms of the antiviral action of the studied drug. First or early stage - an unknown mechanism, possibly related to the effect on cellular receptors. Second or late stage - main antiviral properties probably associated with an interferonogenic effect.