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Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed., Methods: ZnO@TiO 2 @AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs., Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus ( S. aureus ), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae ( S. pneumoniae ) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus , and S. pneumoniae were 50 μg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs., Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Bai et al.)

Background: Zinc oxide nanoparticles (ZnO NPs) has been widely used in various fields and has had an important impact on human public health. In addition, it inevitably damages human health, including neurological diseases. Therefore, this study explored the effect of ZnO NPs on epilepsy., Methods: The effect of ZnO NPs on epilepsy was observed by behavioral analysis. TLR4 expression and autophagy related pathways were detected by RNA-seq and Western blot. In addition, the cell types of autophagy were detected by immunofluorescence. Further, the electrophysiological changes of ZnO NPs induced autophagy were detected by whole-cell patch-clamp. Finally, the recovery experiment was carried out by TLR4 inhibitor (TAK-242)., Results: We found that ZnO NPs enhanced epilepsy susceptibility and severity. Through RNA-seq analysis and Western blot, it was found that ZnO NPs affected the changes of TLR4 and autophagy related pathways. In addition, we found that ZnO NPs mainly affects autophagy of inhibitory neurons, resulting in excitation/inhibition imbalance. The autophagy and epileptic phenotypes were reversed with TAK-242. In general, ZnO NPs exacerbate epileptic seizures by modulating the TLR4-autophagy axis., Conclusion: ZnO NPs enhanced the susceptibility and severity of epilepsy. Mechanistically, ZnO NPs affected autophagy by changing the expression of TLR4. In particular, the ZnO NPs mainly affected the synaptic function of inhibitory neuron, leading to excitation/inhibition imbalances., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Ke et al.)

Purpose: The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin., Methods: In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase ( Aanat ), melatonin receptor1A ( Mt1 / Mtnr1a ), melatonin receptor1B ( Mt2 / Mtnr1b ), and neuropeptide Y ( Npy ) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed., Results: The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat , the membrane receptors Mt1 and Mt2 and Npy during the day and night., Conclusion: Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity., Competing Interests: The authors report no competing interests related to this study., (© 2023 Yang et al.)

Introduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15-24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action., Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats., Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 - 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ-induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing., Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Yadav et al.)

Introduction: Zinc oxide nanoparticles (ZnO NPs) participate in all aspects of our lives, but with their wide application, more and more disadvantages are exposed. The goal of this study was to investigate the toxicity of ZnO NPs in female mice ovaries and explore its potential mechanism., Methods: In this study, adult female mice were orally exposed to 0, 100, 200, and 400 mg/kg ZnO NPs for 7 days. We explored the underlying mechanisms via the intraperitoneal injection of N-acetyl-cysteine (NAC), an inhibitor of oxidative stress, and salubrinal (Sal), an inhibitor of endoplasmic reticulum (ER) stress., Results: The results indicated that serum estradiol and progesterone levels declined greatly with increasing ZnO NPs dosage. Hematoxylin and eosin (HE) staining revealed increased atretic follicles and exfoliated follicular granulosa cells. Moreover, at the transcriptional level, antioxidant-related genes such as Keap1 and Nrf2 , and ER stress-related genes PERK, eIF2α , and ATF4 were markedly upregulated. In addition, the expression of Caspase12, Caspase9 , and Caspase3 , which are genes related to apoptosis, was also upregulated in all ZnO NPs treatment groups. Serum malondialdehyde (MDA) content was remarkably up-regulated, whereas superoxide dismutase (SOD) activity was down-regulated. The 400 mg/kg ZnO NPs treatment group suffered the most substantial harm. However, ovarian damage was repaired when NAC and Sal were added to this group., Conclusion: ZnO NPs had toxic effects on the ovary of female mice, which were due to oxidative stress, ER stress, and the eventual activation of apoptosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Xu et al.)

Introduction: Zinc oxide nanoparticles (ZnO NPs) show anti-cancer activity. Diffuse Large B-cell Lymphoma (DLBCL) is a type of B-cell malignancies with unsatisfying treatment outcomes. This study was set to assess the potential of ZnO NPs to selectively induce apoptosis in human DLBCL cells (OCI-LY3), and to describe possible molecular mechanisms of action., Methods: The impact of ZnO NPs on DLBCL cells and normal peripheral blood mononuclear cells (PBMCs) was studied using cytotoxicity assay and flow-cytometry. Transcriptomics analysis was conducted to identify ZnO NPs-dependent changes in the transcriptomic profiles of DLBCL cells., Results: ZnO NPs selectively induced apoptosis in DLBCL cells, and caused changes in their transcriptomes. Deferential gene expression (DGE) with fold change (FC) ≥3 and p ≤ 0.008 with corrected p ≤ 0.05 was identified for 528 genes; 125 genes were over-expressed and 403 genes were under-expressed in ZnO NPs-treated DLBCL cells. The over-expressed genes involved in biological processes and pathways like stress response to metal ion, cellular response to zinc ion, metallothioneins bind metals, oxidative stress, and negative regulation of growth. In contrast, the under-expressed genes were implicated in DNA packaging complex, signaling by NOTCH, negative regulation of gene expression by epigenetic, signaling by WNT, M phase of cell cycle, and telomere maintenance. Setting the FC to ≥1.5 with p ≤ 0.05 and corrected p ≤ 0.1 showed ZnO NPs to induce over-expression of anti-oxidant genes and under-expression of oncogenes; target B-cell receptor (BCR) signaling pathway and NF-κB pathway; and promote apoptosis by intrinsic and extrinsic pathways., Discussion: Overall, ZnO NPs selectively induced apoptosis in DLBCL cells, and possible molecular mechanisms of action were described., Competing Interests: The author declares that there are no conflicts of interest., (© 2022 Alsagaby.)

Background: Periimplantitis is continuously one of major threats for the uneventful functioning of dental implants. Current approaches of drug delivery systems are being more commonly implemented into oral- and maxillofacial biomaterials in order to decrease the risk of implant failure due to bacterial infection. Silver nanoparticles and their compounds have been proven in eradicating oral bacteria responsible for peri-implant infections. Nevertheless, their evaluation as coating for implant abutments has not been extensively evaluated so far. This article describes a novel coating consisting of zinc oxide (ZnO) and silver (Ag) nanoparticles (NPs). This coating was used to modify healing abutments that could be used as drug delivery systems in oral implantology., Materials and Method: Nanoparticles with a ZnO + 0.1% Ag composition were produced by microwave solvothermal synthesis and then incorporated into the surface of titanium healing abutments by high-power ultrasonic deposition. Surface morphology, roughness, wettability were evaluated. Ability of biofilm formation inhibition was tested against S. mutans, S. oralis, S. aureus and E. coli ., Results: ZnO+0.1%Ag NPs were sufficiently deposed on the surface of the abutments creating nanostructured coating which increased surface roughness and decreased wettability. Modified abutments significantly decreased bacterial biofilm formation. Bacteria present in SEM studies were unlikely to settle and replicate on the experimental abutments as their cells were rounded, insufficiently spread on the surface and covered with released NPs., Conclusion: Experimental nanostructured abutments were easily manufactured by high-power ultrasonic deposition and provided significant antibacterial properties. Such biomaterials could be used as temporary drug delivery abutments for prevention and treatment of intra- and extraoral peri-implant infections in the area of the head and neck., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Pokrowiecki et al.)

Introduction: Plumbago indica L. is considered a valuable source in the Plumbaginaceae family for various types of active compound such as alkaloids, phenolics and saponins. To promote the usage of P. indica in the bionanotechnology field, zinc oxide nanoparticles (ZnONPs) were biosynthesized by using its alcoholic extract. The inhibitory effects of ZnONPs and the plant extract were also evaluated against HSV-1., Methods: ZnONPs were described by the following techniques, UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and x-ray diffraction (XRD). The phenolic and flavonoid contents of P. indica extract, which are accountable for bioreduction, formation and stabilization of the nanoparticles, were analyzed by HPLC technique. The antiviral assessment was implemented on both agents by using Vero cell lines., Results: DLS revealed that the average size of ZnONPs was 32.58 ± 7.98 nm and the zeta potential was -20.8 mV. The observation of TEM analysis revealed that the particle size of ZnONPs varied from 2.56 to 8.83 nm. The XRD analysis verified the existence of pure crystals of hexagonal shapes of nanoparticles of ZnO with a main average size of 35.28 nm that is approximating to the values of particle size acquired by SEM analysis (19.64 and 23.21 nm). The HPLC analysis of P. indica ethanolic extract showed that gallic acid, chlorogenic acid and rutin were the major compounds, with concentrations equal to 8203.99, 2965.95 and 1144.99 µg/g, respectively. Regarding the antiviral assessment, the synthesized uncalcinated ZnONPs were found to exhibit a promising activity against HSV-1, with CC 50 and IC 50 values equal to 43.96 ± 1.39 and 23.17 ± 2.29 µg/mL, respectively., Conclusion: The green synthesized ZnONPs are considered promising adjuvants to enhance the efficacy of HSV-1 drugs., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Melk et al.)

Introduction: As a biofilm-associated disease, dental caries benefits from nanoparticle (NP)-based therapies. Streptococcus mutans ( S. mutans ) is a primary aetiologic agent for dental caries development. We successfully applied a synergistic therapy of Ag/ZnO nanocomposites combined with light-emitting diode (LED) radiation to inhibit S. mutans biofilms. However, the antibiofilm mechanism has not been fully elucidated, and little is known about the biofilm formation ability of bacteria that survive NP-based therapies., Methods: This study explored the antibiofilm formation mechanism of this synergistic therapy by an integrated approach based upon proteomics., Results: Synergistic therapy killed 99.8% of bacteria, while the biofilm formation ability of 0.2% surviving bacteria was inhibited. The proteomic responses of S. mutans to synergistic therapy were comprehensively characterized to unveil the mechanism of bacterial death and biofilm formation inhibition of the surviving bacteria. In total, 55 differentially expressed proteins (12 upregulated and 43 downregulated) were recorded. The bioinformatic analysis demonstrated that cellular integrity damage and regulated expression of structure-associated proteins were the main reasons for bacterial death. In addition, the proteomic study indicated the potential inhibition of metabolism in surviving bacteria and provided a biofilm-related network consisting of 17 differentially expressed proteins, explaining the multiantibiofilm formation actions. Finally, we reported and verified the inhibitory effects of synergistic therapy on sucrose metabolism and D-alanine metabolism, which disturbed the biofilm formation of surviving bacteria., Conclusion: Our findings demonstrated that synergistic therapy killed most bacteria and inhibited the surviving bacteria from forming biofilms. Furthermore, the antibiofilm formation mechanism was revealed by proteomics analysis of S. mutans after synergistic therapy and subsequent metabolic studies. Our success may provide a showcase to explore the antibiofilm formation mechanism of NP-based therapies using proteomic studies., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Jiang et al.)

Purpose: The present study deals with the in vitro evaluation of the potential use of coordination compound-based zinc oxide (ZnO) nanoparticles (NPs) for the treatment of triple negative breast cancer cells (TNBrCa). As BrCa is one of the most prevalent cancer types and TNBrCa treatment is difficult due to poor prognosis and a high metastasis rate, finding a more reliable treatment option should be of the utmost interest., Methods: Prepared by reacting zinc carboxylates (formate, acetate, propionate, butyrate, isobutyrate, valerate) and hexamethylenetetramine, 4 distinct coordination compounds were further subjected to two modes of conversion into ZnO NPs - ultrasonication with oleic acid or heating of pure precursors in an air atmosphere. After detailed characterization, the resulting ZnO NPs were subjected to in vitro testing of cytotoxicity toward TNBrCa and normal breast epithelial cells. Further, their biocompatibility was evaluated., Results: The resulting ZnO NPs provide distinct morphological features, size, biocompatibility, and selective cytotoxicity toward TNBrCa cells. They internalize into two types of TNBrCa cells and imbalance their redox homeostasis, influencing their metabolism, morphology, and ultimately leading to their death via apoptosis or necrosis., Conclusion: The crucial properties of ZnO NPs seem to be their morphology, size, and zinc content. The ZnO NPs with the most preferential values of all three properties show great promise for a future potential use in the therapy of TNBrCa., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Stepankova et al.)

Purpose: Nanomaterials for antimicrobial applications have gained interest in recent years due to the increasing bacteria resistance to conventional antibiotics. Wound sterilization, water treatment and surface decontamination all avail from multifunctional materials that also possess excellent antibacterial properties, eg zinc oxide (ZnO). Here, we assess and compare the effects of synthesized hedgehog-like ZnO structures and commercial ZnO particles with and without mixing on the inactivation of bacteria on surfaces and in liquid environments., Methods: Gram-positive ( Staphylococcus aureus ) and Gram-negative ( Escherichia coli ) bacteria in microbial culture medium were added to reverse spin bioreactors that contained different concentrations of each ZnO type to enable dynamic mixing of the bacteria-ZnO suspensions. Optical density of the bacteria-ZnO suspensions was measured in real-time and the number of viable bacteria after 24 h exposure was determined using standard microbiological techniques. The concentration of zinc ion generated from ZnO dissolution in different liquid types was estimated from the dynamic interaction exposure. Static antibacterial tests without agitation in liquid media and on agar surface were performed for comparison., Results: A correlation between increasing ZnO particle concentration and reduction in viable bacteria was not monotonous. The lowest concentration tested (10 µg/mL) even stimulated bacteria growth. The hedgehog ZnO was significantly more antibacterial than commercial ZnO particles at higher concentrations (up to 1000 µg/mL tested), more against E. coli than S. aureus . Minimum inhibitory concentration in microwell plates was correlated with those results. No inhibition was detected for any ZnO type deposited on agar surface. Zinc ion release was greatly suppressed in cultivation media. Scanning electron microscopy images revealed that ZnO needles can pierce membrane of bacteria whereas the commercial ZnO nanoparticles rather agglomerate on the cell surface., Conclusion: The inhibition effects are thus mainly controlled by the interaction dynamics between bacteria and ZnO, where mixing greatly enhances antibacterial efficacy of all ZnO particles. The efficacy is modulated also by ZnO particle shapes, where hedgehog ZnO has superior effect, in particular at lower concentrations. However, at too low concentrations, ZnO can stimulate bacteria growth and must be thus used with caution., Competing Interests: Dr Júlia Mičová reports grants from Scientific Grant Agency of Ministry of Education, Science, Research and Sport of Slovak Republic and Slovak Academy of Sciences, during the conduct of the study. Professor Bohuslav Rezek reports grants from Czech Science Foundation and Ministry of Education, Youth and Sports of the Czech Republic, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2021 Rutherford et al.)

Background: Therapeutic selectivity and drug resistance are critical issues in cancer therapy. Currently, zinc oxide nanoparticles (ZnO NPs) hold considerable promise to tackle this problem due to their tunable physicochemical properties. This work was designed to prepare SnO 2 -doped ZnO NPs/reduced graphene oxide nanocomposites (SnO 2 -ZnO/rGO NCs) with enhanced anticancer activity and better biocompatibility than those of pure ZnO NPs., Materials and Methods: Pure ZnO NPs, SnO 2 -doped ZnO (SnO 2 -ZnO) NPs, and SnO 2 -ZnO/rGO NCs were prepared via a facile hydrothermal method. Prepared samples were characterized by field emission transmission electron microscopy (FETEM), energy dispersive spectroscopy (EDS), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), ultraviolet-visible (UV-VIS) spectrometer, and dynamic light scattering (DLS) techniques. Selectivity and anticancer activity of prepared samples were assessed in human breast cancer (MCF-7) and human normal breast epithelial (MCF10A) cells. Possible mechanisms of anticancer activity of prepared samples were explored through oxidative stress pathway., Results: XRD spectra of SnO 2 -ZnO/rGO NCs confirmed the formation of single-phase of hexagonal wurtzite ZnO. High resolution TEM and SEM mapping showed homogenous distribution of SnO 2 and rGO in ZnO NPs with high quality lattice fringes without any distortion. Band gap energy of SnO 2 -ZnO/rGO NCs was lower compared to SnO 2 -ZnO NPs and pure ZnO NPs. The SnO 2 -ZnO/rGO NCs exhibited significantly higher anticancer activity against MCF-7 cancer cells than those of SnO 2 -ZnO NPs and ZnO NPs. The SnO 2 -ZnO/rGO NCs induced apoptotic response through the upregulation of caspase-3 gene and depletion of mitochondrial membrane potential. Mechanistic study indicated that SnO 2 -ZnO/rGO NCs kill cancer cells through oxidative stress pathway. Moreover, biocompatibility of SnO 2 -ZnO/rGO NCs was also higher against normal breast epithelial (MCF10A cells) in comparison to SnO 2 -ZnO NPs and ZnO NPs., Conclusion: SnO 2 -ZnO/rGO NCs showed enhanced anticancer activity and better biocompatibility than SnO 2 -ZnO NPs and pure ZnO NPs. This work suggested a new approach to improve the selectivity and anticancer activity of ZnO NPs. Studies on antitumor activity of SnO 2 -ZnO/rGO NCs in animal models are further warranted., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Ahamed et al.)

Purpose: To evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action., Materials and Methods: Three-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally., Results: The high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P<0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P>0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P<0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P>0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P<0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P<0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P<0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P<0.05), whereas RANKL expression did not change significantly (P>0.05)., Conclusion: We infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Xu et al.)

Purpose: The study aimed to find an effective method for fungal-mediated synthesis of zinc oxide nanoparticles using endophytic fungal extracts and to evaluate the efficiency of synthesized ZnO NPs as antimicrobial and anticancerous agents., Methods: Zinc oxide nanoparticles (ZnO NPs) were produced from zinc nitrate hexahydrate with fungal filtrate by the combustion method. The spectroscopy and microscopy techniques, such as ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX), dynamic light scattering (DLS), and transmission electron microscopy (TEM) with selected area electron diffraction (SAED), were used to characterize the obtained product. Antibacterial activity on Gram-positive ( Staphylococcus aureus and Bacillus cereus ) and Gram-negative ( Pseudomonas aeruginosa and Escherichia coli ) samples was tested by broth microplate dilution technique. ZnO NPs antifungal activity was determined against plant pathogenic and regular contaminating fungi using the food-poison method. The anticancerous assay of the synthesized ZnO NPs was also investigated by cell uptake, MTT assay, and apoptosis assay., Results: The fungal synthesized ZnO NPs were pure, mainly hexagonal in shape and size range of 34-55 nm. The biosynthesized ZnO NPs could proficiently inhibit both Gram-positive and Gram-negative bacteria. ZnO NPs synthesized from fungal extract exhibited antifungal activity in a dose-dependent manner with a high percentage of mycelial inhibition. The cell uptake analysis of ZnO NPs suggests that a significant amount of ZnO NPs (1 μg/mL) was internalized without disturbing cancer cells' morphology. As a result, the synthesized ZnO NPs showed significant anticancer activity against cancer cells at 1 μg/mL concentration., Conclusion: This fungus-mediated synthesis of ZnO NPs is a simple, eco-friendly, and non-toxic method. Our results show that the synthesized ZnO NPs are an excellent novel antimicrobial and anticancer agent. Further studies are required to understand the mechanism of the antimicrobial, anticancerous action of ZnO NPs and their possible genotoxicity., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Sumanth et al.)

Purpose: To study the cytotoxic evaluation, antimicrobial and confocal analysis of zinc oxide nanoparticles (ZnO NPs) obtained from a novel plant product fennel ( Foeniculum vulgare Mill.) seed extract (FSE)., Methods: ZnO NPs were analyzed using UV-Vis spectroscopy, XRD, FTIR, TEM and EDX techniques. The MTT cell cytotoxicity assay measured the proliferation and survival of MCF-7 cells treated at different concentrations of FSE-derived ZnO NPs. The antimicrobial activity towards pathogenic bacteria and yeast strains was investigated., Results: The UV-Vis spectra showed two peaks at 438 nm and 446 nm, confirming nanoparticle formation. The SEM morphology results showed porous ranging from 23-51 nm. The antitumor activity value (IC 50 ) was at 50 µg/mL and 100 µg/mL. Besides, morphological changes of MCF-7, cells treated at different concentrations of FSE of ZnO NPs were observed in cell cultures transfected with a transient pCMV6-XL4-GFP-expressing vector containing C-terminal domain GFP-tagged proteins, which resulted in an apoptotic effect. Antimicrobial IZ ranged up No Inhibition to 18.00 ± 0.4. The IZ revealed at the highest concentration was E. faecium VRE and yeast Cryptococcus sp. (18.00 ± 0.4. mm), followed by S. aureus (17.00 ± 0.2 mm) and P. aeruginosa and the yeast C. parapsilosis (16 ± 0.4 mm). The IZ was equal to that caused by the nystatin to Cryptococcus sp., which was significantly highest than ampicillin treatments of S. aureus, P. aeruginosa, C. albicans , and C. parapsilosis . The MIC value of the FSE-derived ZnO NPs tested against E.faecium and C.albicans was 6.00 µg/mL ( E. faecium and C. albicans ). It was 32.00 µg/mL ( S. aureus, S. typhimurium and Cryptococcus sp.), 64.00 µg/mL ( P. aeruginosa ), and 128 µg/mL ( C. parapsilosis )., Conclusion: As far as it is to our knowledge, this study established, for the first time, the biological activities of biosynthesized ZnO NPs from FSE and their synergistic therapeutic potential., Competing Interests: There are no conflicts of interest for the authors., (© 2020 AlSalhi et al.)

Introduction: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach., Objective: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action., Methods: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells., Results: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells ( p ≤0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥4 and p ≤0.008 with corrected p ≤0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in "response to zinc", "response to toxic substance" and "negative regulation of growth" (corrected p ≤0.05). In contrast, the repressed genes positively regulated "cell proliferation", "cell migration", "cell adhesion", "receptor signaling pathway via JAK-STAT" and "phosphatidylinositol 3-kinase signaling" (corrected p ≤0.05). Lowering the FC to ≥1.5 with p ≤0.05 and corrected p ≤0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway., Conclusion: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells., Competing Interests: The authors declare no conflicts of interest for this work., (© 2020 Alsagaby et al.)

Prosthesis-associated infections and aseptic loosening are major causes of implant failure. There is an urgent need to improve the antibacterial ability and osseointegration of orthopedic implants. Zinc oxide nanoparticles (ZnO-NPs) are a common type of zinc-containing metal oxide nanoparticles that have been widely studied in many fields, such as food packaging, pollution treatment, and biomedicine. The ZnO-NPs have low toxicity and good biological functions, as well as antibacterial, anticancer, and osteogenic capabilities. Furthermore, ZnO-NPs can be easily obtained through various methods. Among them, green preparation methods can improve the bioactivity of ZnO-NPs and strengthen their potential application in the biological field. This review discusses the antibacterial abilities of ZnO-NPs, including mechanisms and influencing factors. The toxicity and shortcomings of anticancer applications are summarized. Furthermore, osteogenic mechanisms and synergy with other materials are introduced. Green preparation methods are also briefly reviewed., Competing Interests: The authors declare that they have no competing interests., (© 2020 Li et al.)

Aim: This study was conducted to evaluate the effects of three nanoparticle solutions used as dentin pretreatments on the microshear bond strength (µSBS) of a conventional glass ionomer cement (GIC) to dentin., Materials and Methods: Ninety intact human molars were used after sectioning their occlusal surfaces to expose flat dentin surfaces. The specimens were randomly assigned to nine groups (n = 10). Group A was the control group (without using the cavity disinfectant). In groups B, C, D, and E, the prepared dentin surfaces were treated with 1 cc 2% chlorhexidine (CHX), 0.1% silver nanoparticle (SNP), 0.1% titanium dioxide nanoparticle (TNP), and 0.1% zinc oxide nanoparticle (ZNP) solutions for 1 minute, respectively, before applying the conditioner. CHX, SNPs, TNPs, and ZNPs were applied for 1 minute after applying the conditioner in groups F, G, H, and I, respectively. The specimens were restored with a conventional GIC and underwent µSBS testing after 24 hours. The data were analyzed using the one-way analysis of variance and Tukey's test (p=0.05)., Results: The applications of the nanoparticles (SNP, TNP, and ZNP) after the conditioner were associated with significantly greater µSBS values compared to that of the control group (p values < 0.05). Significantly higher µSBS values were observed when TNP or ZNP was applied after the conditioner compared to their applications before the conditioner (p values < 0.05). The highest µSBS values were observed when TNP was applied after the conditioner., Conclusion: Dentin pretreatment with the nanoparticles after applying the conditioner enhanced the bond strength of the GIC to dentin compared with the control group. The best results were obtained for the TNPs applied after the conditioner., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Jowkar et al.)

Purpose: Zinc oxide nanoparticles (nZnO) have been widely used in the medicine field. Numerous mechanistic studies for nZnO's anticancer effects are merely performed under high concentration exposure. However, possible anticancer mechanisms of epigenetic dysregulation induced by low doses of nZnO are unclear., Methods: nZnO were characterized and bladder cancer T24 cells were treated with nZnO for 48 hrs at different exposure concentrations. Cell cycle, apoptosis, cell migration and invasion were determined. We performed qRT-PCR, Western blot and chromatin immunoprecipitation to detect the mRNA and protein levels of signaling pathway cascades for histone modification., Results: In this study, we investigated the potential anticancer effects and mechanisms of nZnO on histone modifications in bladder cancer T24 cells upon low-dose exposure. Our findings showed that low concentrations of nZnO resulted in cell cycle arrest at S phase, facilitated cellular late apoptosis, repressed cell invasion and migration after 48 hrs exposure. These anticancer effects could be attributed to increased RUNX3 levels resulting from reduced H3K27me 3 occupancy on the RUNX3 promoter, as well as decreased contents of histone methyltransferase EZH2 and the trimethylation of histone H3K27. Our findings reveal that nZnO are able to enter into the cytoplasm and nucleus of T24 cells. Additionally, both particles and ions from nZnO may jointly contribute to the alteration of histone methylation. Moreover, sublethal nZnO-conducted anticancer effects and epigenetic mechanisms were not associated with oxidative stress or DNA damage., Conclusion: We reveal a novel epigenetic mechanism for anticancer effects of nZnO in bladder cancer cells under low-dose exposure. This study will provide experimental basis for the toxicology and cancer therapy of nanomaterials., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhang et al.)

Background: Developing an ideal wound dressing that meets the multiple demands of safe and practical, good biocompatibility, superior mechanical property and excellent antibacterial activity is highly desirable for wound healing. Bacterial cellulose (BC) is one of such promising class of biopolymers since it can control wound exudates and can provide moist environment to a wound resulting in better wound healing. However, the lack of antibacterial activity has limited its application., Methods and Results: We prepared a flexible dressing based on a bacterial cellulose membrane and then modified it by chemical crosslinking to prepare in situ synthesis of nZnO/BCM via a facile and eco-friendly approach. Scanning electron microscopy (SEM) results indicated that nZnO/BCM membranes were characterized by an ideal porous structure (pore size: 30~ 90 μm), forming a unique string-beaded morphology. The average water vapor transmission of nZnO/BCM was 2856.60 g/m 2 /day, which improved the moist environment of nZnO/BCM. ATR-FITR further confirmed the stepwise deposition of nano-zinc oxide. Tensile testing indicated that our nanocomposites were flexible, comfortable and resilient. Bacterial suspension assay and plate counting methods demonstrated that 5wt. % nZnO/BCM possessed excellent antibacterial activity against S.aureus and E. coli , while MTT assay demonstrated that they had no measurable cytotoxicity toward mammalian cells. Moreover, skin irritation test and histocompatibility examination supported that 5wt. % nZnO/BCM had no stimulation to skin and had acceptable biocompatibility with little infiltration of the inflammatory cells. Finally, by using a bacteria-infected ( S. aureus and E. coli ) murine wound model, we found that nZnO/BCM could prevent in vivo bacterial infections and promote wound healing via accelerating the re-epithelialization and wound contraction, and these membranes had no obvious toxicity toward normal tissues., Conclusion: Therefore, the constructed nZnO/BCM has great potential for biomedical applications as an efficient antibacterial wound dressing., Competing Interests: Prof. Dr. Hai Lin reports a patent for the preparation and application of bacterial cellulose wound dressing with anti-bacterial property licensed to 201510301459X. The authors report no other conflicts of interest in this work., (© 2020 Luo et al.)

The inappropriate use of antimicrobials has resulted in the selection of resistant strains. Thus, a great number of studies have focused on the investigation of new antimicrobial agents. The use of zinc oxide nanoparticles (ZnO NPs) to optimise the fight against microbial resistance has been receiving increased attention due to the non-specific activity of inorganic antimicrobial agents. The small particle size and the high surface area of ZnO NPs can enhance antimicrobial activity, causing an improvement in surface reactivity. In addition, surface modifiers covering ZnO NPs can play a role in mediating antimicrobial activity since the surface properties of nanomaterials alter their interactions with cells; this may interfere with the antimicrobial effect of ZnO NPs. The possibility of using surface modifiers with groups toxic to microorganisms can improve the antimicrobial activity of ZnO NPs. Understanding the exact toxicity mechanisms is crucial to elucidating the antimicrobial activity of ZnO NPs in bacteria and fungi. Therefore, this review aims to describe the mechanisms of ZnO NPs toxicity against fungi and bacteria and how the different structural and physical-chemical characteristics of ZnO NPs can interfere in their antimicrobial activity., Competing Interests: The authors have declared no conflict of interest in this work., (© 2019 Lallo da Silva et al.)

Background: Zinc oxide nanoparticles (ZnO NPs) are used in modern cancer therapy based on their specific target, efficacy, low toxicity and biocompatibility. The photocatalytic performance of Zinc oxide (ZnO) nanocomposites with hyaluronic acid (HA) was used to study anticancer properties against various human cancer cell lines., Methods: Zinc oxide (ZnO) nanocomposites functionalized by hyaluronic acid (HA) were prepared by a co-precipitation method (HA-ZnONcs). The submicron-flower-shaped nanocomposites were further functionalized with ginsenoside Rh2 by a cleavable ester bond via carbodiimide chemistry to form Rh2HAZnO. The physicochemical behaviors of the synthesized ZnO nanocomposites were characterized by various analytical and spectroscopic techniques. We carried out 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the toxicity of Rh2HAZnO in various human cancer cells (A549, MCF-7, and HT29). Furthermore, to confirm the apoptotic effects of Rh2HAZnO and to determine the role of the Caspase-9/p38 MAPK pathways by various molecular techniques such as RT-PCR and Western blotting. Furthermore, Rh2HAZnO induced morphological changes of these cell lines, mainly intracellular reactive oxygen species (ROS) were observed by ROS staining and nucleus by Hoechst staining., Results: We confirmed that Rh2HAZnO exhibits the anti-cancer effects on A549 lung cancer, HT29 colon cancer, and MCF7 breast cancer cells. Moreover, intracellular reactive oxygen species (ROS) were observed in three cancer cell lines. Rh2HAZnO induced apoptotic process through p53-mediated pathway by upregulating p53 and BAX and downregulating BCL2. Specifically, Rh2HAZnO induced activation of cleaved PARP (Asp214) in A549 lung cancer cells and upregulated Caspase-9/phosphorylation of p38 MAPK in other cell lines (HT29 and MCF-7). Furthermore, Rh2HAZnO induced morphological changes in the nucleus of these cell lines., Conclusion: These results suggest that the potential anticancer activity of novel Rh2HAZnO nanoparticles might be linked to induction of apoptosis through the generation of ROS by activation of the Caspase-9/p38 MAPK pathway., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Kim et al.)

Introduction: Nanoparticles (NPs) can be toxic due to their nano-range sizes. Zinc oxide (ZnO) has good biocompatibility and is commercially used in cosmetics. Moreover, ZnO NPs have potential biomedical uses, but their safety remains unclear., Methods: A range of doped ZnO NPs was evaluated for antileishmanial activity and in vitro toxicity in brine shrimp and human macrophages, and N-doped ZnO NPs were evaluated for in vivo toxicity in male BALB/C mice. N-doped ZnO NPs were administered via two routes: intra-peritoneal injection and topically as a paste. The dosages were 10, 50, and 100 mg/kg/day for 14 days., Results: Topical administration was safe at all dosages, but intra-peritoneal injection displayed toxicity at higher doses, namely, 50 and 100 mg/kg/day. The pathological results for the i.p. dose groups were mild to severe degenerative changes in parenchyma cells, increases in Kupffer cells, disappearance of hepatic plates, increases in cell size, ballooning, cytoplasmic changes, and nuclear pyknosis in the liver. Kidney histology was also altered in the i.p. administration group (dose 100 mg/kg/day), with inflammatory changes in the focal area. We associate pathological abnormalities with the presence of doped ZnO NPs at the diseased site, which was verified by PIXE analysis of the liver and kidney samples of the treated and untreated mice groups., Conclusion: The toxicity of the doped ZnO NPs can serve as an essential determinant for the effects of ZnO NPs on environmental toxicity and can be used for guidelines for safer use of ZnO-based nanomaterials in topical treatment of leishmaniasis and other biomedical applications., Competing Interests: The authors report no conflicts of interest related to this work., (© 2019 Nazir et al.)

Background: Recently, several studies demonstrate the possible role of zinc oxide (ZnO) in the protection of several skin diseases, but less is known about the role of ZnO nanoparticles in the inflammatory skin disease. So, this study was designed to confirm the pivotal role of the nano zinc oxide cream in the alleviation of lead oxide (PbO) induced-allergic dermatitis in rats., Materials and Methods: Two concentrations (1% and 6%) of ZnONPs creams were prepared and characterized prior to being used in the study. A total number of 30 male Wistar rats were randomly divided into six groups. Group 1 (negative control), groups 2&3 (either 1% or 6% ZnONPs control groups), group 4 (PbO), groups 5&6 (co-treatment of each ZnONPs concentration+PbO). All rats in different groups were observed daily to determine the severity of dermal gross lesions. Histopathological studies, mRNA analysis, and oxidative stress evaluations were performed on the affected skin tissue. Immunohistochemical studies were performed to evaluate the expression of cluster of differentiation CD4, CD8 and intercellular adhesion molecules ICAM-1 in different groups., Results: PbO caused extensive skin oxidative damage manifested by a significant increase in MDA level with a decrease in GSH content and CAT activity. The results of histopathological and immunohistochemical examinations revealed that topical application of PbO for 14 days led to severe allergic dermatitis with remarkable elevations in the number of CD4+ T-helper, CD8+ T-cytotoxic lymphocytes, and ICAM-1 expression. On the other hand, noticeable improvements were recorded in all the previous toxicopathological parameters among the groups treated by either 1% or 6% ZnO-NPs cream. However, the best results were observed in the group treated with 1% ZnO-NPs cream., Conclusion: Our findings suggest that 1% of ZnO-NPs cream is safe when applied topically on the inflamed skin. Moreover, it had anti-inflammatory and antioxidant effects so that, it is recommended to use the 1% ZnO-NPs cream to avert the dermal toxicity-induced by PbO., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Khalaf et al.)

Purpose: To investigate the effects of zinc oxide nanoparticles (ZnO NPs) on chloroquine (CQ)-induced itching, and overall behavior of mice after oral administration of ZnO NPs of various sizes and doses. Background: With the wide-spread use of ZnO NPs in pharmaceuticals and cosmetics, concerns about their safety and toxicity are also increasing. Multiple aspects of ZnO NPs regarding cytotoxicity and tolerability are under investigation globally. Still, a clear conclusion about their safety has not been reached. Chloroquine phosphate is an antimalarial with known side effects of itching in humans and animals. In this study, CQ was used to induce itching in mice, and the effects of ZnO NPs on scratching and other neurological behavior of mice were observed. Methods: Female BALB/c mice were divided into eleven groups of six mice each. ZnO NPs of various sizes and doses were administered orally 1 hour before CQ (32 mg/kg body weight) was administered subcutaneously. The effect of ZnO NPs on CQ-induced pruritus was observed for the next 30 minutes. Simultaneously, overall behavioral changes (socialization and locomotion) were also recorded using a video camera. Results: A significant reduction ( P ˂0.001) in scratching bouts was observed at all three doses of ZnO NPs (particle sizes 100, 30 nm, and green synthesized 30 nm). Locomotion was reduced significantly ( P ˂0.001) in ZnO NPs-treated groups in comparison to normal saline and CQ group, additionally, a significant increase in socialization ( P ˂0.05) was observed in ZnO NP-treated groups as compared to CQ group. Conclusion: ZnO NPs, instead of aggravating the dermatological condition, ameliorated the pruritus. All sizes of ZnO NPs used significantly improved socialization among mice and reduced locomotion activity., Competing Interests: The authors report no conflicts of interest in this work.

Background: Zinc oxide (ZnO) nanoparticles and their networks have been developed for use in various applications such as gas sensors and semiconductors., Aim: In this study, their antibacterial activity against Escherichia coli under dual ultraviolet (UV) irradiation for disinfection was investigated., Materials and Methods: ZnO nanoparticles were synthesized and immobilized onto silicon (Si) wafers by self-assembly. The physicochemical properties and antibacterial activity of ZnO nanoparticles and their networks were evaluated. Gene ontology was analyzed and toxicity levels were also monitored., Results: Synthesized ZnO nanoparticles were spherical nanocrystals (<100 nm; Zn, 47%; O, 53%) that formed macro-mesoporous three-dimensional nanostructures on Si wafers in a concentration-dependent manner. ZnO nanoparticles and their networks on Si wafers had an excellent antibacterial activity against E. coli under dual UV irradiation (>3log CFU/mL). Specifically, arrayed ZnO nanoparticle networks showed superior activity compared with free synthesized ZnO nanoparticles. Oxidative stress-responsive proteins in E. coli were identified and categorized, which indicated antibacterial activity. Synthesized ZnO nanoparticles were less cytotoxic in HaCaT with an IC50 of 6.632 mg/mL, but phototoxic in Balb/c 3T3., Conclusion: The results suggested that ZnO nanoparticles and their networks can be promising photocatalytic antibiotics for use in next-generation disinfection systems. Their application could also be extended to industrial and clinical use as effective and safe photocatalytic antibiotics., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The increasing resistance of pathogenic bacteria to antibiotics is a challenging worldwide health problem that has led to the search for new and more efficient antibacterial agents. Nanotechnology has proven to be an effective tool for the fight against bacteria., Methods: In this paper, we present the synthesis and traits of trimetal (CuZnFe) oxide nanoparticles (NPs) using X-ray diffraction, high-resolution transmission electron microscopy, and energy dispersive x-ray spectroscopy. We evaluated the antibacterial activity of these NPs against gram-negative Escherichia coli and gram-positive Enterococcus faecalis and then compared it to that of their pure single-metal oxide components CuO and ZnO., Results: Our study showed that the antibacterial activity of the trimetal oxide NPs was greater against E . coli than against E . faecalis . Overall, the antimicrobial effect of trimetal NPs is between those of pure ZnO and CuO nanoparticles, which may mean that their cytotoxicity is also between that of pure ZnO and CuO NPs, making them potential antibiotics. However, the cytotoxicity of trimetal NPs to mammalian cells needs to be verified., Conclusion: The combination of three metal oxide NPs (ZnO, CuO, and Fe 2 O 3 ) in one multimetal (CuZnFe) oxide NPs will enhance the therapeutic strategy against a wide range of microbial infections. Bacteria are unlikely to develop resistance against this new NP because bacteria must go through a series of mutations to become resistant to the trimetal oxide NP. Therefore, this NP can combat existing and emerging bacterial infections., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

In the present study, binary oxide (cadmium oxide [CdO]) x (zinc oxide [ZnO]) 1-x nanoparticles (NPs) at different concentrations of precursor in calcination temperature were prepared using thermal treatment technique. Cadmium and zinc nitrates (source of cadmium and zinc) with polyvinylpyrrolidone (capping agent) have been used to prepare (CdO) x (ZnO) 1-x NPs samples. The sample was characterized by X-ray diffraction (XRD), scanning electron microscopy, energy-dispersive X-ray (EDX), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. XRD patterns analysis revealed that NPs were formed after calcination, which showed a cubic and hexagonal crystalline structure of (CdO) x (ZnO) 1-x NPs. The phase analysis using EDX spectroscopy and FTIR spectroscopy confirmed the presence of Cd and Zn as the original compounds of prepared (CdO) x (ZnO) 1-x NP samples. The average particle size of the samples increased from 14 to 33 nm as the concentration of precursor increased from x=0.20 to x=0.80, as observed by TEM results. The surface composition and valance state of the prepared product NPs were determined by X-ray photoelectron spectroscopy (XPS) analyses. Diffuse UV-visible reflectance spectra were used to determine the optical band gap through the Kubelka-Munk equation; the energy band gap was found to decrease for CdO from 2.92 to 2.82 eV and for ZnO from 3.22 to 3.11 eV with increasing x value. Additionally, photoluminescence (PL) spectra revealed that the intensity in PL increased with an increase in particle size. In addition, the antibacterial activity of binary oxide NP was carried out in vitro against Escherichia coli ATCC 25922 Gram (-ve), Salmonella choleraesuis ATCC 10708, and Bacillus subtilis UPMC 1175 Gram (+ve). This study indicated that the zone of inhibition of 21 mm has good antibacterial activity toward the Gram-positive B. subtilis UPMC 1175., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Metal oxide (MO) nanoparticles have been studied as nano-antibiotics due to their antimicrobial activities even in antibiotic-resistant microorganisms. We hypothesized that a hybrid system of dual UV irradiation and MO nanoparticles would have enhanced antimicrobial activities compared with UV or MO nanoparticles alone. In this study, nanoparticles of ZnO, ZnTiO 3 , MgO, and CuO were selected as model nanoparticles. A dual UV collimated beam device of UV-A and UV-C was developed depending upon the lamp divided by coating. Physicochemical properties of MO nanoparticles were determined using powder X-ray diffractometry (PXRD), Brunauer-Emmett-Teller analysis, and field emission-scanning electron microscopy with energy-dispersive X-ray spectroscopy. Atomic force microscopy with an electrostatic force microscopy mode was used to confirm the surface topology and electrostatic characteristics after dual UV irradiation. For antimicrobial activity test, MO nanoparticles under dual UV irradiation were applied to Escherichia coli and M13 bacteriophage (phage). The UV-A and UV-C showed differential intensities in the coated and uncoated areas (UV-A, coated = uncoated; UV-C, coated ≪ uncoated). MO nanoparticles showed sharp peaks in PXRD patterns, matched to pure materials. Their primary particle sizes were less than 100 nm with irregular shapes, which had an 8.6~25.6 m 2 /g of specific surface area with mesopores of 22~262 nm. The electrostatic properties of MO nanoparticles were modulated after UV irradiation. ZnO, MgO, and CuO nanoparticles, except ZnTiO 3 nanoparticles, showed antibacterial effects on E. coli . Antimicrobial effects on E. coli and phages were also enhanced after cyclic exposure of dual UV and MO nanoparticle treatment using the uncoated area, except ZnO nanoparticles. Our results demonstrate that dual UV-MO nanoparticle hybrid system has a potential for disinfection. We anticipate that it can be developed as a next-generation disinfection system in pharmaceutical industries and water purification systems., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Microbial contamination of different cosmetic preparations, as a result of preservative failure, presents a major public health threat. Also, most of the known preservatives have serious consumer side effects. The antimicrobial activity of zinc oxide nanoparticles (ZnO NP) is well documented. Therefore, we aimed to determine the possible use of unirradiated and γ-irradiated ZnO NP as a cosmetic preservative., Methods: The possible use of ZnO NP as a preservative was tested and compared to commonly used preservatives using a challenge test. Their activity was tested in six different types of preparations. The effect of γ radiation on the antimicrobial activity of ZnO NP was tested through determination of the obtained zone diameters against different microorganisms and the total aerobic microbial count in tested preparations. The antimicrobial activity, of unirradiated and γ-irradiated ZnO NP during storage was also determined., Results: ZnO NP were superior to other commonly used preservatives in all tested cosmetic preparations. They pass the challenge test in all types of tested preparations. γ irradiation enhanced their antimicrobial activity in all tested preparations. The irradiation causes a reduction in NP sizes that is directly proportional to the applied radiation dose. Upon storage, ZnO NP were effective in maintaining the microbial count of the product within the acceptable range. Their activity in stored products was enhanced by γ irradiation., Conclusion: Unirradiated and γ-irradiated ZnO NP can be used as effective preservatives. They are compatible with the components of all tested products. γ irradiation enhanced the antimicrobial activity of ZnO NP., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3)., Methods: ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays., Results: Exposure of cells to ZnO NPs resulted in a dose-dependent loss of cell viability, and the characteristic apoptotic features such as rounding and loss of adherence, enhanced reactive oxygen species generation, and loss of mitochondrial membrane potential were observed in the ZnO NP-treated cells. Furthermore, the cells treated with ZnO NPs showed significant double-strand DNA breaks, which are gained evidences from significant number of γ-H 2 AX and Rad51 expressed cells. ZnO NP-treated cells showed upregulation of p53 and LC3, indicating that ZnO NPs are able to upregulate apoptosis and autophagy. Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-H 2 AX, p53, and LC3 and downregulation of Bcl-2., Conclusion: The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Fungal infected denture, which is typically composed of polymethylmethacrylate (PMMA), is a common problem for a denture wearer, especially an elderly patient with limited manual dexterity. Therefore, increasing the antifungal effect of denture by incorporating surface modification nanoparticles into the PMMA, while retaining its mechanical properties, is of interest., Aim of the Study: This study aimed to evaluate antifungal, optical, and mechanical properties of heat-cured PMMA incorporated with different amounts of zinc oxide nanoparticles (ZnOnps) with or without methacryloxypropyltrimethoxysilane modification., Materials and Methods: Specimens made from heat-cured PMMA containing 1.25, 2.5, and 5% (w/w) nonsilanized (Nosi) or silanized (Si) ZnOnps were evaluated. Specimens without filler served as control. The fungal assay was performed placing a Candida albicans suspension on the PMMA surface for 2 h, then Sabouraud Dextrose Broth was added, and growth after 24 h was determined by counting colony forming units on agar plates. A spectrophotometer was used to measure the color in L* (brightness), a* (red-green), b* (yellow-blue) and opacity of the experimental groups. Flexural strength and flexural modulus were determined using a three-point bending test on universal testing machine after 37°C water storage for 48 h and 1 month., Results: The antifungal, optical, and mechanical properties of the PMMA incorporated with ZnOnps changed depending on the amount. With the same amount of ZnOnps, the silanized groups demonstrated a greater reduction in C. albicans compared with the Nosi groups. The color difference (ΔE) and opacity of the Nosi groups were greater compared with the Si groups. The flexural strength of the Si groups, except for the 1.25% group, was significantly greater compared with the Nosi groups., Conclusion: PMMA incorporated with Si ZnOnps, particularly with 2.5% Si ZnOnps, had a greater antifungal effect, less color differences, and opacity compared with Nosi ZnOnps, while retaining its mechanical properties., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1 -/- BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Nanoscale ZnO is one of the best choices for ultraviolet (UV) protection, not only because of its antimicrobial properties but also due to its potential application for UV preservation. However, the behavior of nanostructured thin ZnO films and long-term effects of UV-radiation exposure have not been studied yet. In this study, we investigated the UV-protection ability of sol gel-derived thin ZnO films after different exposure times. Scanning electron microscopy, atomic force microscopy, and UV-visible optical spectroscopy were carried out to study the structure and optical properties of the ZnO films as a function of the UV-irradiation time. The results obtained showed that the prepared thin ZnO films were somewhat transparent under the visible wavelength region and protective against UV radiation. The UV-protection factor was 50+ for the prepared samples, indicating that they were excellent UV protectors. The deposited thin ZnO films demonstrated promising antibacterial potential and significant light absorbance in the UV range. The experimental results suggest that the synthesized samples have potential for applications in the health care field., Competing Interests: The authors report no conflicts of interest in this work.

Zinc oxide (ZnO) is widely incorporated as a food additive in animal diets. In order to optimize the beneficial effects of ZnO and minimize any resultant environmental pollution, ZnO nanoparticles are often used for delivery of the zinc. However, the possible toxic effects of ZnO nanoparticles, including effects on cytochrome P450 (CYP450) enzymes, have not been evaluated. In this study, we investigated the effect of ZnO nanoparticles, in doses used in animal feeds, on CYP450 enzymes, liver and intestinal enzymes, liver and kidney histopathology, and hematologic indices in rats. We found that liver and kidney injury occurred when the concentrations of ZnO nanoparticles in feed were 300-600 mg/kg. Also, liver mRNA expression for constitutive androstane receptor was suppressed and mRNA expression for pregnane X receptor was induced when feed containing ZnO nanoparticles was given at a concentration of 600 mg/kg. Although the expression of mRNA for CYP 2C11 and 3A2 enzymes was induced by ZnO nanoparticles, the activities of CYP 2C11 and 3A2 were suppressed. While liver CYP 1A2 mRNA expression was suppressed, CYP 1A2 activity remained unchanged at all ZnO nanoparticle doses. Therefore, it has been concluded that ZnO nanoparticles, in the doses customarily added to animal feed, changed the indices of hematology and blood chemistry, altered the expression and activity of hepatic CYP enzymes, and induced pathological changes in liver and kidney tissues of rats. These findings suggest that greater attention needs to be paid to the toxic effects of ZnO nanoparticles in animal feed, with the possibility that the doses of ZnO should be reduced.

As an engineered nanomaterial, zinc oxide nanoparticles (ZnO NPs) are used frequently in biological applications and can make contact with human skin. Here, we systematically investigated the effects of ZnO NPs on non-tumorigenic human epidermal keratinocytes, which were used as a test model for this in vitro study, at the epigenetic and molecular levels. Our results showed that ZnO NPs induced cell cycle arrest at the G2/M checkpoint before the viability of human epidermal keratinocytes was reduced, which was associated with the chromatin changes at the epigenetic level, including increased methylation of histone H3K9 and decreased acetylation of histone H4K5 accompanied by chromatin condensation at 24 hours. The mRNA expression of the methyltransferase genes G9a and GLP was also increased upon treatment with ZnO NPs, and the acetyltransferase genes GCN5, P300, and CBP were downregulated. Reactive oxygen species were found to be more abundant after treatment with ZnO NPs for 6 hours, and DNA damage was observed at 24 hours. Transmission electron microscopy and flow cytometry confirmed that ZnO NPs were absorbed into the cell when they were added to the medium. Apoptotic human epidermal keratinocytes were detected, and the expression of the proapoptotic genes Bax, Noxa, and Puma increased significantly, while the expression of the antiapoptotic gene Bcl-xl decreased 24 hours after exposure to ZnO NPs. These findings suggest that the ZnO NPs induced cell cycle arrest at G2/M, which was associated with epigenetic changes and accompanied by p53-Bax mitochondrial pathway-mediated apoptosis.

Lipid and protein oxidation are well-known manifestations of free radical activity and oxidative stress. The current study investigated extermination of Leishmania tropica promastigotes induced by lipid and protein oxidation with reactive oxygen species produced by PEGylated metal-based nanoparticles. The synthesized photodynamic therapy-based doped and nondoped zinc oxide nanoparticles were activated in daylight that produced reactive oxygen species in the immediate environment. Lipid and protein oxidation did not occur in dark. The major lipid peroxidation derivatives comprised of conjugated dienes, lipid hydroperoxides, and malondialdehyde whereas water, ethane, methanol, and ethanol were found as the end products. Proteins were oxidized to carbonyls, hydroperoxides, and thiol degrading products. Interestingly, lipid hydroperoxides were produced by more than twofold of the protein hydroperoxides, indicating higher degradation of lipids compared to proteins. The in vitro evidence represented a significant contribution of the involvement of both lipid and protein oxidation in the annihilated antipromastigote effect of nanoparticles.

Alginate hydrogel/zinc oxide nanoparticles (nZnO) composite bandage was developed by freeze-dry method from the mixture of nZnO and alginate hydrogel. The developed composite bandage was porous with porosity at a range of 60%-70%. The swelling ratios of the bandages decreased with increasing concentrations of nZnO. The composite bandages with nZnO incorporation showed controlled degradation profile and faster blood clotting ability when compared to the KALTOSTAT® and control bandages without nZnO. The prepared composite bandages exhibited excellent antimicrobial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and methicillin resistant S. aureus (MRSA). Cytocompatibility evaluation of the prepared composite bandages done on human dermal fibroblast cells by Alamar assay and infiltration studies proved that the bandages have a non-toxic nature at lower concentrations of nZnO whereas slight reduction in viability was seen with increasing nZnO concentrations. The qualitative analysis of ex-vivo re-epithelialization on porcine skin revealed keratinocyte infiltration toward wound area for nZnO alginate bandages.

In this work, we highlighted the effect of surface modifications of one-dimensional (1D) ZnO nanostructures (NSs) grown by the vapor-solid mechanism on their antibacterial activity. Two sets of ZnO NSs were modified separately - one set was modified by annealing in an Ar environment, and the second set was modified in O2 plasma. Annealing in Ar below 800°C resulted in a compressed lattice, which was due to removal of Zn interstitials and increased O vacancies. Annealing above 1,000°C caused the formation of a new prominent phase, Zn2SiO4. Plasma oxidation of the ZnO NSs caused an expansion in the lattice due to the removal of O vacancies and incorporation of excess O. Photoluminescence (PL) spectroscopy was employed for the quantification of defects associated with Zn and O in the as-grown and processed ZnO NS. Two distinct bands were observed, one in the ultraviolet (UV) region, due to interband transitions, and other in the visible region, due to defects associated with Zn and O. PL confirmed the surface modification of ZnO NS, as substantial decrease in intensities of visible band was observed. Antibacterial activity of the modified ZnO NSs demonstrated that the surface modifications by Ar annealing limited the antibacterial characteristics of ZnO NS against Staphylococcus aureus. However, ZnO NSs annealed at 1,000°C or higher showed a remarkable antibacterial activity against Escherichia coli. O2 plasma-treated NS showed appreciable antibacterial activity against both E. coli and S. aureus. The minimum inhibition concentration was determined to be 0.5 mg/mL and 1 mg/mL for Ar-annealed and plasma-oxidized ZnO NS, respectively. It was thus proved that the O content at the surface of the ZnO NS was crucial to tune the antibacterial activity against both selected gram-negative (E. coli) and gram-positive (S. aureus) bacterial species.

To optimize mesenchymal stem cell differentiation and antibacterial properties of titanium (Ti), nano-sized zinc oxide (ZnO) particles with tunable concentrations were incorporated into TiO2 nanotubes (TNTs) using a facile hydrothermal strategy. It is revealed here for the first time that the TNTs incorporated with ZnO nanoparticles exhibited better biocompatibility compared with pure Ti samples (controls) and that the amount of ZnO (tailored by the concentration of Zn(NO3)2 in the precursor) introduced into TNTs played a crucial role on their osteogenic properties. Not only was the alkaline phosphatase activity improved to about 13.8 U/g protein, but the osterix, collagen-I, and osteocalcin gene expressions was improved from mesenchymal stem cells compared to controls. To further explore the mechanism of TNTs decorated with ZnO on cell functions, a response surface mathematical model was used to optimize the concentration of ZnO incorporation into the Ti nanotubes for stem cell differentiation and antibacterial properties for the first time. Both experimental and modeling results confirmed (R (2) values of 0.8873-0.9138 and 0.9596-0.9941, respectively) that Ti incorporated with appropriate concentrations (with an initial concentration of Zn(NO3)2 at 0.015 M) of ZnO can provide exceptional osteogenic properties for stem cell differentiation in bone cells with strong antibacterial effects, properties important for improving dental and orthopedic implant efficacy.

Nanomedicine has recently emerged as a better option for the treatment of various diseases. Here, we investigated the in vivo anticoccidial properties of zinc oxide nanoparticles (ZNPs). ZNPs were crystalline in nature, with a smooth and spherical surface and a diameter in the range of ~10-15 nm. The X-ray diffraction pattern was utilized to identify the crystalline property of the grown ZNPs, whereas field emission scanning electron microscopy was employed to check the size and morphology of the ZNPs. The data showed that mice infected with Eimeria papillata produced 29.7×10(3)±1,500 oocysts/g feces on day 5 postinfection. This output was significantly decreased, to 12.5×10(3)±1,000 oocysts, in mice treated with ZNPs. Infection also induced inflammation and injury of the jejunum. This was evidenced (1) through an increase in the inflammatory histological score, (2) through increased production of nitric oxide and malondialdehyde, and (3) through a decrease in both the glutathione level and goblet cell number in mice jejuna. All these infection-induced parameters were significantly altered during treatment with ZNPs. Our results indicate, therefore, that ZNPs have protective effects against E. papillata-induced coccidiosis.

A series of novel bionanocomposites were cast using different contents of zinc oxide-silver nanoparticles (ZnO-AgNPs) stabilized by cellulose nanocrystals (CNC) as multifunctional nanosized fillers in poly(vinyl alcohol)/chitosan (PVA/Cs) matrices. The morphological structure, mechanical properties, ultraviolet-visible absorption, and antimicrobial properties of the prepared films were investigated as a function of their CNC/ZnO-AgNP content and compared with PVA/chitosan/CNC bionanocomposite films. X-ray diffraction and field emission scanning electron microscopic analyses showed that the CNC/ZnO-AgNPs were homogeneously dispersed in the PVA/Cs matrix and the crystallinity increased with increasing nanosized filler content. Compared with pure PVA/Cs, the tensile strength and modulus in the films increased from 0.055 to 0.205 GPa and from 0.395 to 1.20 GPa, respectively. Ultraviolet and visible light can be efficiently absorbed by incorporating ZnO-AgNPs into a PVA/Cs matrix, suggesting that these bionanocomposite films show good visibility and ultraviolet-shielding effects. The bionanocomposite films had excellent antimicrobial properties, killing both Gram-negative Salmonella choleraesuis and Gram-positive Staphylococcus aureus. The enhanced physical properties achieved by incorporating CNC/ZnO-AgNPs could be beneficial in various applications.

There has been a significant and growing concern over nosocomial medical device infections. Previous studies have demonstrated that embedding nanoparticles alone (specifically, zinc oxide [ZnO]) in conventional polymers (eg, polyvinyl chloride [PVC]) can decrease bacteria growth and may have the potential to prevent or disrupt bacterial processes that lead to infection. However, little to no studies have been conducted to determine mammalian cell functions on such a nanocomposite material. Clearly, for certain medical device applications, maintaining healthy mammalian cell functions while decreasing bacteria growth is imperative (yet uncommon). For this reason, in the presented study, ZnO nanoparticles of varying sizes (from 10 nm to >200 nm in diameter) and functionalization (including no functionalization to doping with aluminum oxide and functionalizing with a silane coupling agent KH550) were incorporated into PVC either with or without ultrasonication. Results of this study provided the first evidence of greater fibroblast density after 18 hours of culture on the smallest ZnO nanoparticle incorporated PVC samples with dispersion aided by ultrasonication. Specifically, the greatest amount of fibroblast proliferation was measured on ZnO nanoparticles functionalized with a silane coupling agent KH550; this sample exhibited the greatest dispersion of ZnO nanoparticles. Water droplet tests showed a general trend of decreased hydrophilicity when adding any of the ZnO nanoparticles to PVC, but an increase in hydrophilicity (albeit still below controls or pure PVC) when using ultrasonication to increase ZnO nanoparticle dispersion. Future studies will have to correlate this change in wettability to initial protein adsorption events that may explain fibroblast behavior. Mechanical tests also provided evidence of the ability to tailor mechanical properties of the ZnO/PVC nanocomposites through the use of the different ZnO nanoparticles. Coupled with previous antibacterial studies, the present study demonstrated that highly dispersed ZnO/PVC nanocomposite materials should be further studied for numerous medical device applications.

A new organic-inorganic nanohybrid based on zinc-layered hydroxide intercalated with an anti-inflammatory agent was synthesized through direct reaction of salicylic acid at various concentrations with commercially available zinc oxide. The basal spacing of the pure phase nanohybrid was 15.73 Å, with the salicylate anions arranged in a monolayer form and an angle of 57 degrees between the zinc-layered hydroxide interlayers. Fourier transform infrared study further confirmed intercalation of salicylate into the interlayers of zinc-layered hydroxide. The loading of salicylate in the nanohybrid was estimated to be around 29.66%, and the nanohybrid exhibited the properties of a mesoporous-type material, with greatly enhanced thermal stability of the salicylate compared with its free counterpart. In vitro cytotoxicity assay revealed that free salicylic acid, pure zinc oxide, and the nanohybrid have a mild effect on viability of African green monkey kidney (Vero-3) cells.

Highly ionic metal oxide nanostructures are attractive, not only for their physiochemical properties but also for antibacterial activity. Zinc oxide (ZnO) nanostructures are known to have inhibitory activity against many pathogens but very little is known about doping effects on it. The antibacterial activity of undoped ZnO and tin (Sn) doped ZnO nanostructures synthesized by a simple, versatile, and wet chemical technique have been investigated against Escherichia coli, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa bacterial strains. It has been interestingly observed that Sn doping enhanced the inhibitory activity of ZnO against S. aureus more efficiently than the other two bacterial strains. From cytotoxicity and reactive oxygen species (ROS) production studies it is found that Sn doping concentration in ZnO does not alter the cytotoxicity and ROS production very much. It has also been observed that undoped and Sn doped ZnO nanostructures are biosafe and biocompatible materials towards SH-SY5Y Cells. The observed behavior of ZnO nanostructures with Sn doping is a new way to prevent bacterial infections of S. aureus, especially on skin, when using these nanostructures in creams or lotions in addition to their sunscreen property as an ultraviolet filter. Structural investigations have confirmed the formation of a single phase wurtzite structure of ZnO. The morphology of ZnO nanostructures is found to vary from spherical to rod shaped as a function of Sn doping. The excitation absorption peak of ZnO is observed to have a blue shift, with Sn doping leading toward a significant tuning in band gap.

In hospitals and clinics worldwide, medical device surfaces have become a rapidly growing source of nosocomial infections. In particular, patients requiring mechanical ventilation (and, thus, intubation with an endotracheal tube) for extended lengths of time are faced with a high probability of contracting ventilator-associated pneumonia. Once inserted into the body, the endotracheal tube provides a surface to which bacteria can adhere and form a biofilm (a robust, sticky matrix that provides protection against the host immune system and antibiotic treatment). Adding to the severity of this problem is the spread of bacterial genetic tolerance to antibiotics, in part demonstrated by the recent and significant increase in the prevalence of methicillin-resistant Staphylococcus aureus. To combat these trends, different techniques in biomaterial design must be explored. Recent research has shown that nanomaterials (materials with at least one dimension less than 100 nm) may have the potential to prevent or disrupt bacterial processes that lead to infections. In this study, polyvinyl chloride (PVC) taken from a conventional endotracheal tube was embedded with varying concentrations of zinc oxide (ZnO) nanoparticles. S. aureus biofilms were then grown on these nanocomposite surfaces during a 24-hour culture. Following this, biofilms were removed from the surfaces and the number of colony forming units present was assessed. Bacterial proliferation on the samples embedded with the highest concentration of ZnO nanoparticles was 87% less when compared to the control, indicating that this technique is effective at reducing biofilm formation on PVC surfaces without the use of antibiotics.

The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles.

Background: Nanomaterials have emerged as ideal multimodal nanomedicine platforms, each one combining different designs and therapeutic approaches in a single system against cancer. The aim of the current study was to explore the synergistic effect and mechanism of a doxorubicin (Dox)-ZnO nanocomplex as a multimodal drug delivery system, integrating Dox chemotherapy and ZnO-mediated photodynamic therapy, in anticancer therapeutics., Methods: Dox was loaded onto ZnO nanomaterials, forming complexes with the transition metal Zn to yield the Dox-ZnO nanocomplexes. After culture with SMMC-7721 hepatocarcinoma cells, the cellular uptake was quantitatively detected by flow cytometry and visualized by fluorescence microscopy. The synergistic effects of the different anticancer therapeutic modalities on the proliferation of SMMC-7721 hepatocarcinoma cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of B-cell lymphoma 2 protein (Bcl-2), Bcl-2 associated X protein (Bax), caspase 9, and caspase 3 were examined by Western blot, to elucidate the possible molecular mechanisms involved., Results: Our observations demonstrated that Dox-ZnO nanocomplexes could act as an efficient drug delivery system for importing Dox into SMMC-7721 cells, enhancing its potential chemotherapy efficiency by increasing the intracellular concentration of Dox. With the addition of ultraviolet (UV) illumination, the ZnO nanomaterials showed excellent photodynamic therapeutic properties, attacking the cancer cells further. Thus the caspase-dependent apoptosis was synergistically induced, resulting in distinct improvement in anticancer activity., Conclusion: The Dox-ZnO nanocomplex presents a promising multimodal agent for comprehensive cancer treatment.

Background: Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear., Methods and Results: We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells., Conclusion: Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.

This study focused on the effects of zinc oxide nanoparticles (nano-ZnO) on spatial learning and memory and synaptic plasticity in the hippocampus of young rats, and tried to interpret the underlying mechanism. Rats were randomly divided into four groups. Nano-ZnO and phosphate-buffered saline were administered in 4-week-old rats for 8 weeks. Subsequently, performance in Morris water maze (MWM) was determined, and then long-term potentiation (LTP) and depotentiation were measured in the perforant pathway to dentate gyrus (DG) in anesthetized rats. The data showed that, (1) in MWM, the escape latency was prolonged in the nano-ZnO group and, (2) LTP was significantly enhanced in the nano-ZnO group, while depotentiation was barely influenced in the DG region of the nano-ZnO group. This bidirectional effect on long-term synaptic plasticity broke the balance between stability and flexibility of cognition. The spatial learning and memory ability was attenuated by the alteration of synaptic plasticity in nano-ZnO-treated rats.