Antibacterial and antibiofilm effect of Zinc Oxide nanoparticles on P. aeruginosa variants isolated from young patients with cystic fibrosis.

BACKGROUND: P. aeruginosa, a biofilm-forming bacteria, is the main cause of pulmonary infection in CF patients. We applied ZnO-np as a therapeutic agent for eradicating multi-drug resistance and biofilm-forming P. aeruginosa isolated from young CF patients. METHODS: A total of 73 throat and sputum samples taken from young CF patients were inquired. ZnO-np was synthesized and characterized in terms of size, shape, and structure for anti-bacterial activity. The antibiotic susceptibility of isolates before and after the addition of 16 µg/ml of ZnO was evaluated using disc diffusion and microtiter methods, respectively. The gene expression level of QS genes was assessed after treatment with 16 µg/ml ZnO-np. RESULTS: The optimum concentration of ZnO-np with a higher inhibitory zone was 16 µg/ml (MIC) and 32 µg/ml (MBC). All isolates were resistant to applied antibiotics, and about 45 % of isolates were strong biofilm-forming bacteria. After treatment with 16 µg/ml ZnO-np, all strains became susceptible to the applied antibiotic except for amikacin, which confers an intermediate pattern. About 63 % and 20 % of isolates were, respectively, non-biofilm and weak biofilm-forming bacteria following the addition of ZnO-np. Relative gene expression of gacA, lasR, and rhlR genes were downregulated significantly (P < 0.001). Although the retS did not have a significant reduction (P = 0.2) CONCLUSION: ZnO-np at a concentration of 16 µg/ml could significantly reduce the P. aeruginosa infection by altering the antibiotic susceptibility pattern and inhibiting biofilm formation. Due to their photocatalytic properties and their ability to penetrate the extracellular polysaccharide layer, ZnO nanoparticles can produce ROS, which increases their susceptibility to antibiotics. Nasal delivery of ZnO-np in the form of aerosol can be considered a potential strategy to decrease the mortality rate in CF patients at an early age.

Study of ZnO nanoparticle-doped dental adhesives on enamels with fluorosis: Electron microscopy, elemental composition and shear bond strength analysis.

This study aimed to evaluate dental adhesives containing different concentrations of zinc oxide nanoparticles (ZnO-NPs) for their use in the treatment of dental fluorosis, observe the interaction of the adhesive on healthy enamel surfaces and with mild and moderate fluorosis, measure the adhesive strength and fluorosis, and determine the phosphorus (P) and calcium (Ca) content on these surfaces, as a reference for the potential use of this adhesive with ZnO-NPs for dental fluorosis treatment. Transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) were used to characterise the ZnO-NPs and analyse the weight percentages of P and Ca in the enamel using X-ray energy dispersive spectroscopy (EDS) and the adhesive strength using a universal mechanical testing machine. FESEM characterisation revealed that the ZnO-NPs were less than 100 nm in size, with quasi-spherical and hexagonal prism shapes. The synthesis of the ZnO-NPs was confirmed by TEM, revealing their hexagonal crystalline structure. The adhesive strength by the universal mechanical testing machine showed that the adhesive with a 3% wt. concentration of ZnO-NPs was better in the three groups of teeth, showing higher adhesive strength in teeth with mild (15.15 MPa) and moderate (12.76 MPa) fluorosis surfaces, and was even higher than that in healthy teeth (9.65 MPa). EDS analysis showed that teeth with mild and moderate fluorosis had the highest weight percentages of P and Ca, but there were no statistically significant differences compared to healthy teeth and teeth treated with adhesives. Lay description: This study focused on testing a new dental adhesive containing small particles called ZnO nanoparticles (ZnO-NPs). This study aimed to demonstrate whether this adhesive with ZnO-NPs could be useful for treating dental fluorosis by improving its adhesion to teeth. One of the first objectives was to determine whether the dental adhesive could adhere better to teeth affected by mild or moderate fluorosis than to healthy teeth by measuring whether the levels of two important elements for healthy teeth, calcium (Ca) and phosphorus (P), were affected by the adhesive. The size and shape of the small particles and teeth with mild or moderate fluorosis were observed using scanning electron microscopy. The nanoparticles were small (< 100 nm) and had specific quasi-spherical and hexagonal prismatic shapes. More damage to the enamel was observed in teeth with mild or moderate fluorosis than in healthy teeth. The adhesive strength test demonstrated that the dental adhesive with 3% ZnO-NPs had the best adhesion on all healthy conditions of teeth. It was particularly effective in teeth with mild or moderate fluorosis. Finally, the evaluation of the levels of P and Ca on the enamel showed that teeth with fluorosis had higher levels of these elements, but using the dental adhesive with ZnO-NPs did not change the levels of these elements significantly because the adhesive avoided greater detachment because of greater adhesion to these surfaces. In conclusion, adding these small particles to dental adhesives could be an option for treating teeth affected by fluorosis. It stuck well and did not affect the levels of the important elements in the teeth.

Green fabrication of ZnO nanoparticles via spirulina platensis and its efficiency against biofilm forming pathogens.

Excessive consumption of antibiotics is considered one of the top public health threats, this necessitates the development of new compounds that can hamper the spread of infections. A facile green technology for the biosynthesis of Zinc oxide nanoparticles (ZnO NPs) using the methanol extract of Spirulina platensis as a reducing and stabilizing agent has been developed. A bunch of spectroscopic and microscopic investigations confirmed the biogenic generation of nano-scaled ZnO with a mean size of 19.103 ± 5.66 nm. The prepared ZnO NPs were scrutinized for their antibacterial and antibiofilm potentiality, the inhibition zone diameters ranged from 12.57 ± 0.006 mm to 17.33 ± 0.006 mm (at 20 µg/mL) for a variety of Gram-positive and Gram-negative pathogens, also significant eradication of the biofilms formed by Staphylococcus aureus and Klebsiella pneumoniae by 96.7% and 94.8% respectively was detected. The free radical scavenging test showed a promising antioxidant capacity of the biogenic ZnO NPs (IC50=78.35 µg/mL). Furthermore, the anti-inflammatory role detected using the HRBCs-MSM technique revealed an efficient stabilization of red blood cells in a concentration-dependent manner. In addition, the biogenic ZnO NPs have significant anticoagulant and antitumor activities as well as minimal cytotoxicity against Vero cells. Thus, this study offered green ZnO NPs that can act as a secure substitute for synthetic antimicrobials and could be applied in numerous biomedical applications.

Biosynthesis and antibacterial activity of ZnO nanoparticles usingBuchanania obovatafruit extract and the eutectic-based ionic liquid.

The fruit extract ofBuchanania obovataand the eutectic-based ionic liquid were utilized, in an eco-friendly, inexpensive, simple method, for synthesizing zinc oxide nanoparticles (ZnO NPs). The influence of the reducing, capping and stabilizing agents, in both mediums, on the structure, optical, and morphological properties of ZnO NPs was extensively investigated. The surface plasmon resonance peaks were observed at 340 nm and 320 nm for the fruit-based and the eutectic-based ionic liquid mediums, respectively, indicating the formation of ZnO NPs. XRD results confirmed the wurtzite structure of the ZnO NPs, exhibiting hexagonal phases in the diffraction patterns. The SEM and TEM images display that the biosynthesized ZnO NPs exhibit crystalline and hexagonal shape, with an average size of 40 nm for the fruit-based and 25 nm for the eutectic-based ionic liquid. The Brunauer-Emmett-Teller (BET) surface area analysis, revealed a value ∼13 m2g-1for ZnO NPs synthesized using the fruit extract and ∼29 m2g-1for those synthesized using the eutectic-based ionic liquid. The antibacterial activity of the biosynthesized ZnO NPs was assessed against clinically isolated Gram-negative (E. coli) and Gram-positive (S. aureus) bacterial strains using the inhibition zone method. The ZnO NPs produced from the eutectic-based ionic liquids confirmed superior antibacterial activity against bothS. aureusandE. colicompared to those mediated by the utilized fruit extract. At a concentration of 1000, the eutectic-based ionic liquid mediated ZnO NPs displayed a maximum inhibition zone of 16 mm againstS. aureus, while againstE. coli, a maximum inhibition zone of 15 mm was observed using the fruit extract mediated ZnO NPs. The results of this study showed that the biosynthesized ZnO NPs can be utilized as an efficient substitute to the frequently used chemical drugs and covering drug resistance matters resulted from continual usage of chemical drugs by users.

ZnO-Salen NPs Employed as Chemosensor for Detection of Al3+ and K+ in Aqueous Medium, Developing Human Cell Images.

ZnO nanoparticles (NPs) were prepared and characterized by different analytical methods and then they were used to decorate with N, N´-bis(salicylidene)ethylenediamine (salen) in order to perform as receptor for the metal ions in an aqueous medium. The results show that ZnO-salen selectively detects Al3+ ions in aqueous medium since the intensity of fluorescence has been enhanced significantly. However, the presence of K+ in the medium further intensified the fluorescence emission for the [ZnO-salen-Al3+] system. The above system has been applied to recognize Al3+ and K+ in cells by developing the cell images, for which, the fluorescence image is brightened if a human glioblastoma U251 cell contains [ZnO-salen-Al3+] + K+ ions, consisting of the fluorescence titration. The binding global constant for Al3+ and the subsequent recognition of K+ by ZnO-salen resulted in ß2(Al3+) = 6.61 × 103 and ß2(K+) = 3.71 × 103 with a detection limit of 36.51 µM for Al3+ and 17.39 µM for K+. In the cell toxicity analysis, the cell viability was over 85% for the ZnO-salen even in the concentration as high as 100 mM.

Novel Chitosan-ZnO nanocomposites derived from Nymphaeaceae fronds for highly efficient removal of Reactive Blue 19, Reactive Orange 16, and Congo Red dyes.

The primary aim of this investigation was to synthesise novel adsorbent by incorporating greenly synthesized zinc oxide nanoparticles into chitosan matrix (G-ZnO-Cs). The production of ZnO Nanoparticles via a green approach involved the utilization of extracts derived from Nymphaeaceae fronds. This assertion was substantiated by the application of Field Emission Scanning Electron Microscopy (FESEM) and X-ray Diffraction (XRD) analytical techniques. Several Analytical methods such as Fourier Transform Infrared spectroscopy (FT-IR), Energy Dispersive X-ray Analysis (EDAX), FESEM, Thermogravimetric Analysis (TGA), XRD, Brunauer-Emmett-Teller (BET) analysis, and point-of-zero charge determination were used to characterize G-ZnO-Cs. Further study investigates the impact of five key processing parameters, namely pH, interaction duration, G-ZnO-Cs dosage, temperature, and initial concentration of dyes, on the removal of three organic dyes Reactive Blue 19 (RB 19), Reactive Orange 16 (RO 16), and Congo Red (CR) The adsorption process of Reactive Blue 19 (RB 19), Reactive Orange 16 (RO 16), and Congo Red (CR) dyes on G-ZnO-Cs were determined to comply to the pseudo-second-order (PSO) and Langmuir models, as determined through equilibrium and kinetic experiments. The highest adsorption capabilities for RB 19, RO 16 and CR dye were revealed to be 219.6 mg/g, 129.6 mg/g, and 118.8 mg/g, respectively. The elimination success rate of the fixed-bed column approach for treating huge volumes was highlighted in the conducted research. Moreover, the G-ZnO-Cs composite exhibited significant reusability due to its ability to undergo elution and simultaneous regeneration processes.

Neuroprotective effect of biogenically synthesized ZnO nanoparticles against oxidative stress and ß-amyloid toxicity in transgenic Caenorhabditis elegans.

Amyloid ß (Aß) plaque accumulation-mediated neuronal toxicity has been suggested to cause synaptic damage and consequent degeneration of brain cells in Alzheimer's disease (AD). With the increasing prerequisite of eco-friendly nanoparticles (NPs), research investigators are utilizing green approaches for the synthesis of zinc oxide (ZnO) NPs for pharmaceutical applications. In this present study, ZnO NPs were synthesized from Acanthus ilicifolius to assess the neuroprotective properties in the AD model of transgenic Caenorhabditis elegans strains CL2006 and CL4176 expressing Aß aggregation. Our findings revealed that the therapeutic effect of green-synthesized ZnO NPs is associated with antioxidant activity. We also found that ZnO NPs significantly enhance the C. elegan's lifespan, locomotion, pharyngeal pumping, chemotaxis behavior also diminish the ROS deposition and intracellular productionMoreover, thioflavin T staining demonstrated that ZnO NPs substantially attenuated the Aß deposition in the C. elegans strain as compared to untreated worms. With their antioxidant properties, the greenly synthesized ZnO NPs had a significant neuroprotective efficiency on Aß-induced toxicity by reducing Aß aggregation and specifically reducing the progression of paralysis in the C. elegans AD model. Our findings suggested that the biosynthesized ZnO NPs could be thought-provoking candidates for age-associated neurodegenerative disorders accompanied by oxidative stress.

Epigallocatechin gallate alleviated the in vivo toxicity of ZnO nanoparticles to mouse intestine.

To evaluate the oral toxicity of nanoparticles (NPs), it is necessary to consider the interactions between NPs and nutrient molecules. Recently, we reported that epigallocatechin gallate (EGCG), a healthy component in green tea, alleviated the toxicity of ZnO NPs to 3D Caco-2 spheroids in vitro. The present study investigated the combined effects of EGCG and ZnO NPs to mice in vivo. Mice were administrated with 35 or 105 mg/kg bodyweight ZnO NPs with or without the presence of 80 mg/kg bodyweight EGCG via gastric route, once a day, for 21 days, and the influences of EGCG on the toxicity of ZnO NPs to intestine were investigated. We found that EGCG altered the colloidal properties of ZnO NPs both in water and artificial intestine juice. As expected, ZnO NPs induced toxicological effects, such as decreased bodyweight, higher Chiu's scores, and ultrastructural changes in intestine, whereas EGCG alleviated these effects. Combined exposure to EGCG and ZnO NPs also changed trace element levels in mouse intestine. For example, the levels of Ti, Co, and Ni were only significantly elevated after co-exposure to EGCG and ZnO NPs, and Fe levels were only significantly decreased by ZnO NPs. Western blot analysis suggested that tight junction (TJ) and endoplasmic reticulum (ER) proteins were elevated by ZnO NPs, but EGCG inhibited this trend. Combined, these data suggested that gastric exposure to ZnO NPs induced intestinal damage, trace element imbalance, and TJ/ER protein expression in mouse intestine, whereas EGCG alleviated these effects of ZnO NPs.

Effects of particle size on toxicity, bioaccumulation, and translocation of zinc oxide nanoparticles to bok choy (Brassica chinensis L.) in garden soil.

The indiscriminate use of zinc oxide nanoparticles (ZnO NPs) in daily life can lead to their release into soil environment. These ZnO NPs can be taken up by crops and translocated to their edible part, potentially causing risks to the ecosystem and human health. In this study, we conducted pot experiments to determine phytotoxicity, bioaccumulation and translocation depending on the size (10 - 30 nm, 80 - 200 nm and 300 nm diameter) and concentration (0, 100, 500 and 1000 mg Zn/kg) of ZnO NPs and Zn ion (Zn2+) in bok choy, a leafy green vegetable crop. After 14 days of exposure, our results showed that large-sized ZnO NPs (i.e., 300 nm) at the highest concentration exhibited greater phytotoxicity, including obstruction of leaf and root weight (42.5 % and 33.8 %, respectively) and reduction of chlorophyll a and b content (50.2 % and 85.2 %, respectively), as well as changes in the activities of oxidative stress responses compared to those of small-sized ZnO NPs, although their translocation ability was relatively lower than that of smaller ones. The translocation factor (TF) values decreased as the size of ZnO NPs increased, with TF values of 0.68 for 10 - 30 nm, 0.55 for 80 - 200 nm, and 0.27 for 300 nm ZnO NPs, all at the highest exposure concentration. Both the results of micro X-ray fluorescence (µ-XRF) spectrometer and bio-transmission electron microscopy (bio-TEM) showed that the Zn elements were mainly localized at the edges of leaves exposed to small-sized ZnO NPs. However, the Zn elements upon exposure to large-sized ZnO NP were primarily observed in the primary veins of leaves in the µ-XRF data, indicating a limitation in their ability to translocate from roots to leaves. This study not only advances our comprehension of the environmental impact of nanotechnology but also holds considerable implications for the future of sustainable agriculture and food safety.

Antioxidant response to ZnO nanoparticles in juvenile Takifugu obscurus: protective effects of salinity.

The extensive utilization of Zinc Oxide nanoparticles (ZnO NPs) has garnered significant attention due to their detrimental impacts on ecosystem. Unfortunately, ecotoxicity of ZnO NPs in coastal waters with fluctuating salinity has been disregarded. This study mainly discussed the toxic effects of ZnO NPs on species inhabiting the transition zones between freshwater and brackish water, who are of great ecological and economic importance among fish. To serve as the model organism, Takifugu obscurus, a juvenile euryhaline fish, was exposed to different ZnO NPs concentrations (0-200 mg/L) and salinity levels (0 and 15 ppt). The results showed that a moderate increase in salinity (15 ppt) could alleviate the toxic effect of ZnO NPs, as evidenced by improved survival rates. The integrated biomarker response index on oxidative stress also revealed that the toxicity of ZnO NPs was higher in freshwater compared to brackish water. These outcomes can be attributed to higher salinity (15 ppt) reducing the bioavailability of ZnO NPs by facilitating their aggregation and inhibiting the release of metal ions. It is noteworthy that elevated salinity was found to alleviate ZnO NPs toxicity by means of osmotic adjustment via the activation of Na+/K+-ATPase activity. This study demonstrates the salinity-dependent effect of ZnO NPs on T. obscurus, suggesting the possibility for euryhaline fish like T. obscurus to adapt their habitat towards more saline environments, under constant exposure to ZnO NPs.

Comparison of biosynthetic zinc oxide nanoparticle and glucantime cytotoxic effects on Leishmania major (MRHO/IR/75/ER).

Currently, zinc oxide (ZnO) particles are used in nanotechnology to destroy a wide range of microorganisms. Although pentavalent antimony compounds are used as antileishmanial drugs, they are associated with several limitations and side effects. Therefore, it is always desirable to try to find new and effective treatments. The aim of this research is to determine the antileishmanial effect of ZnO particles in comparison to the Antimoan Meglumine compound on promastigotes and amastigotes of Leishmania major (MRHO/IR/75/ER). After the extraction and purification of macrophages from the peritoneal cavity of C57BL/6 mice, L. major parasites were cultured in Roswell Park Memorial Institute-1640 culture medium containing fetal bovine serum (FBS) 10% and antibiotic. In this experimental study, the effect of different concentrations of nanoparticles was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) colorimetric method, in comparison to the glucantime on promastigotes, amastigotes and healthy macrophages in the culture medium. The amount of light absorption of the obtained color from the regeneration of tetrazolium salt to the product color of formazan by the parasite was measured by an enzyme-linked immunosorbent assay (ELISA) reader, and the IC50 value was calculated. IC50 after 24 h of incubation was calculated as IC50 = 358.6 µg/mL. The results showed, that the efficacy of ZnO nanoparticles was favorable and dose-dependent. The concentration of 500 µg/mL of ZnO nanoparticles induced 84.67% apoptosis after 72. Also, the toxicity of nanoparticles was less than the drug. Nanoparticles exert their cytotoxic effects by inducing apoptosis. They can be suitable candidates in the pharmaceutical industry in the future.

Inulin-Coated ZnO Nanoparticles: A Correlation between Preparation and Properties for Biostimulation Purposes.

Within the framework of plant biostimulation, a pivotal role is played by the achievement of low-cost, easily prepared nanoparticles for priming purposes. Therefore, in this report, two different synthetic strategies are described to engineer zinc oxide nanoparticles with an inulin coating. In both protocols, i.e., two-step and gel-like one-pot protocols, nanoparticles with a highly pure ZnO kernel are obtained when the reaction is carried out at T ≥ 40 °C, as ascertained by XRD and ATR/FTIR studies. However, a uniformly dispersed, highly homogeneous coating is achieved primarily when different temperatures, i.e., 60 °C and 40 °C, are employed in the two phases of the step-wise synthesis. In addition, a different binding mechanism, i.e., complexation, occurs in this case. When the gel-like process is employed, a high degree of coverage by the fructan is attained, leading to micrometric coated aggregates of nanometric particles, as revealed by SEM investigations. All NPs from the two-step synthesis feature electronic bandgaps in the 3.25-3.30 eV range in line with previous studies, whereas the extensive coating causes a remarkable 0.4 eV decrease in the bandgap. Overall, the global analysis of the investigations indicates that the samples synthesized at 60 °C and 40 °C are the best suited for biostimulation. Proof-of-principle assays upon Vicia faba seed priming with Zn5 and Zn5@inu indicated an effective growth stimulation of seedlings at doses of 100 mgKg-1, with concomitant Zn accumulation in the leaves.

Tunable Construction of Chiral Nematic Cellulose Nanocrystals/ZnO Films for Ultra-Sensitive, Recyclable Sensing of Humidity and Ethanol.

The investigation of functional materials derived from sustainable and eco-friendly bioresources has generated significant attention. Herein, nanocomposite films based on chiral nematic cellulose crystals (CNCs) were developed by incorporating xylose and biocompatible ZnO nanoparticles (NPs) via evaporation-induced self-assembly (EISA). The nanocomposite films exhibited iridescent color changes that corresponded to the birefringence phenomenon under polarized light, which was attributed to the formation of cholesteric structures. ZnO nanoparticles were proved to successfully adjust the helical pitches of the chiral arrangements of the CNCs, resulting in tunable optical light with shifted wavelength bands. Furthermore, the nanocomposite films showed fast humidity and ethanol stimuli response properties, exhibiting the potential of stimuli sensors of the CNC-based sustainable materials.

miRNA-driven sensitization of breast cancer cells to Doxorubicin treatment following exposure to low dose of Zinc Oxide nanoparticles.

The impact of Engineered nanomaterials (ENMs) (i.e., Zinc Oxide nanoparticles (ZnO NPs)) on human health has been investigated at high and unrealistic exposure levels, overlooking the potential indirect harm of subtoxic and long exposures. Therefore, this study aimed to investigate the impacts of subtoxic concentrations of zinc oxide (ZnO NPs) on breast cancer cells' response to Doxorubicin. Zinc oxide nanoparticles caused a concentration-dependent reduction of cell viability in multiple breast cancer cell lines. A subtoxic concentration of 1.56 µg/mL (i.e., no observed adverse effect level) was used in subsequent mechanistic studies. Molecularly, miRNA profiling revealed significant downregulation of 13 oncogenic miRNAs (OncomiRs) in cells exposed to the sub-toxic dose of ZnO NPs followed by doxorubicin treatment. Our comprehensive bioinformatic analysis has identified 617 target genes enriched in ten pathways, mainly regulating gene expression and transcription, cell cycle, and apoptotic cell death. Several tumor suppressor genes emerged as validated direct targets of the 13 OncomiRs, including TFDP2, YWHAG, SMAD2, SMAD4, CDKN1A, CDKN1B, BCL2L11, and TGIF2. This study insinuates the importance of miRNAs in regulating the responsiveness of cancer cells to chemotherapy. Our findings further indicate that being exposed to environmental ENMs, even at levels below toxicity, might still modulate cancer cells' response to chemotherapy, which highlights the need to reestablish endpoints of ENM exposure and toxicity in cancer patients receiving chemotherapeutics.

Starch-based antibacterial food packaging with ZnO nanoparticle.

Starch-based biofilms with embedded nanoparticles (NPs) are used to wrap food in biodegradable packaging system that has high antibacterial action against a variety of microorganisms. In this study, ZnO NPs were synthesised using both a green synthesis approach utilising Azadirachta indica (Neem) and a chemical synthesis approach using the sol-gel technique. The structural and morphological properties of all synthesized NPs were characterized through XRD, UV-VIS, UV-DRS, FTIR, and FESEM analysis. Further, these NPs were employed in the development of starch-based biodegradable films. A meticulous comparative analysis was performed to evaluate the functional properties of the nanocomposites, encompassing crucial parameters such as film thickness, moisture content, swelling index, opacity, solubility, water vapor permeability, and tensile strength. In comparison to films embedded with chemically synthesised NPs (F1), nanocomposite with green synthesised NPs (F2) showed 15.27% greater inhibition against Escherichia coli growth and 22.05% stronger inhibition against Staphylococcus aureus bacterial strains. Based on the biodegradability analysis, the nanocomposite film-F2 showed a 53.33% faster degradation rate compared to the film-F1. The developed films were utilized to assess the quality of both wrapped and unwrapped grapes, leading to the generalization of the research for the development of starch-based antibacterial and environmentally friendly food packaging material. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05834-9.

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy.

Although the neurotoxicity of ZnO nanoparticles (NPs) has been evaluated in animal and nerve cell culture models, these models cannot accurately mimic human brains. Three-dimensional (3D) brain organoids based on human-induced pluripotent stem cells have been developed to study the human brains, but this model has rarely been used to evaluate NP neurotoxicity. We used 3D brain organoids that express cortical layer proteins to investigate the mechanisms of ZnO NP-induced neurotoxicity. Cytotoxicity caused by high levels of ZnO NPs (64 µg/mL) correlated with high intracellular Zn ion levels but not superoxide levels. Exposure to a non-cytotoxic concentration of ZnO NPs (16 µg/mL) increased the autophagy-marker proteins LC3B-II/I but decreased p62 accumulation, whereas a cytotoxic concentration of ZnO NPs (64 µg/mL) decreased LC3B-II/I proteins but did not affect p62 accumulation. Fluorescence micro-optical sectioning tomography revealed that 64 µg/mL ZnO NPs led to decreases in LC3B proteins that were more obvious at the outer layers of the organoids, which were directly exposed to the ZnO NPs. In addition to reducing LC3B proteins in the outer layers, ZnO NPs increased the number of micronuclei in the outer layers but not the inner layers (where LC3B proteins were still expressed). Adding the autophagy flux inhibitor bafilomycin A1 to ZnO NPs increased cytotoxicity and intracellular Zn ion levels, but adding the autophagy inducer rapamycin only slightly decreased cellular Zn ion levels. We conclude that high concentrations of ZnO NPs are cytotoxic to 3D brain organoids via defective autophagy and intracellular accumulation of Zn ions.

Sparked ZnO nanoparticles-based electrochemical sensor for onsite determination of glyphosate residues.

Glyphosate (N-(phosphonomethyl)glycine) is well known nonselective and broad-spectrum herbicide that has been extensively used in agricultural areas around the world to increase agricultural productivity. However, the utilization of glyphosate can cause environmental contamination and health problems. Therefore, the detection of glyphosate with a fast, low-cost, and portable sensor is still important. In this work, the electrochemical sensor has been developed by modifying of working surface on the screen-printed silver electrode (SPAgE) with a mixtures solution between zinc oxide nanoparticles (ZnO-NPs) and poly(diallyldimethylammonium chloride) (PDDA) by the drop-casting process. The ZnO-NPs have been prepared based on a sparking method by using pure zinc wires. The ZnO-NPs/PDDA/SPAgE sensor shows a wide range of glyphosate detection (0µM-5 mM). The limit of detection of ZnO-NPs/PDDA/SPAgE is 2.84µM. The ZnO-NPs/PDDA/SPAgE sensor exhibits high selective towards glyphosate with minimal interference from other commonly used herbicides including paraquat, butachlor-propanil and glufosinate-ammonium. Furthermore, the ZnO-NPs/PDDA/SPAgE sensor demonstrates a good estimation of glyphosate concentration in real samples such as green tea, corn juice and mango juice.

Particle Size Determines the Phytotoxicity of ZnO Nanoparticles in Rice (Oryza sativa L.) Revealed by Spatial Imaging Techniques.

To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.

Application of ZnO Nanoparticles Encapsulated in Mesoporous Silica on the Abaxial Side of a Solanum lycopersicum Leaf Enhances Zn Uptake and Translocation via the Phloem.

Foliar application of nutrient nanoparticles (NPs) is a promising strategy for improving fertilization efficiency in agriculture. Phloem translocation of NPs from leaves is required for efficient fertilization but is currently considered to be feasible only for NPs smaller than a cell wall pore size exclusion limit of <20 nm. Using mass spectrometry imaging, we provide here the first direct evidence for phloem localization and translocation of a larger (∼70 nm) fertilizer NP comprised of ZnO encapsulated in mesoporous SiO2 (ZnO@MSN) following foliar deposition. The Si content in the phloem tissue of the petiole connected to the dosed leaf was ∼10 times higher than in the xylem tissue, and ∼100 times higher than the phloem tissue of an untreated tomato plant petiole. Direct evidence of NPs in individual phloem cells has only previously been shown for smaller NPs introduced invasively in the plant. Furthermore, we show that uptake and translocation of the NPs can be enhanced by their application on the abaxial (lower) side of the leaf. Applying ZnO@MSN to the abaxial side of a single leaf resulted in a 56% higher uptake of Zn as well as higher translocation to the younger (upper) leaves and to the roots, than dosing the adaxial (top) side of a leaf. The higher abaxial uptake of NPs is in alignment with the higher stomatal density and lower density of mesophyll tissues on that side and has not been demonstrated before.

Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer's disease via acetylcholinesterase inhibition and oxidative stress reduction.

Alzheimer's disease (AD) is one of the primary health problems linked to the decrease of acetylcholine in cholinergic neurons and elevation in oxidative stress. Myco-fabrication of ZnO-NPs revealed excellent biological activities, including anti-inflammatory and acetylcholinesterase inhibitory potentials. This study aims to determine if two distinct doses of myco-fabricated ZnO-NPs have a positive impact on behavioral impairment and several biochemical markers associated with inflammation and oxidative stress in mice that have been treated by aluminum chloride (AlCl3) to induce AD. Sixty male mice were haphazardly separated into equally six groups. Group 1 was injected i.p. with 0.5 ml of deionized water daily during the experiment. Mice in group 2 received AlCl3 (50 mg/kg/day i.p.). Groups 3 and 4 were treated i.p. with 5 and 10 mg/kg/day of ZnO-NPs only, respectively. Groups 5 and 6 were given i.p. 5 and 10 mg/kg/day ZnO-NPs, respectively, add to 50 mg/kg/day AlCl3. Results showed that the AlCl3 caused an increase in the escape latency time and a reduction in the time spent in the target quadrant, indicating a decreased improvement in learning and memory. Moreover, acetylcholinesterase enzyme (AChE) activity and malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin 1ß (IL-1ß) levels were significantly increased, and the content of glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), as well as levels of serotonin and dopamine, were decreased in brain tissues only in AlCl3 treated mice. However, treatment of mice with myco-fabrication of ZnO-NPs at doses of 5 or 10 mg/kg improves learning and memory function through ameliorate all the previous parameters in the AD mice group. The low dose of 5 mg/kg is more effective than a high dose of 10 mg/kg. In accordance with these findings, myco-fabricated ZnO-NPs could enhance memory and exhibit a protective influence against memory loss caused by AlCl3.