Cytotoxicity Of ZnO Nanoparticles Research Articles

The efficacy of ZnO-NPs prepared via green route against colon and breast cancer cells

This study is an attempt to utilize green tea [GT] extract and pomegranate peel [PP] for the synthesis of zinc oxide nanoparticles. The selected plants are rich in phenols therefore are awaited to successfully synthesize ZnO nanoparticles without the need for an alkylating agent. In addition, these extracts contain various functional groups that confer colloidal stability for nanoparticles and ameliorate their biocompatibility via a one pot synthesis route. X-ray diffraction analysis (XRD), and transmission electron microscopy (TEM) techniques are used to investigate both structural and morphological properties of the obtained nanoparticles [Zn-GT and Zn-PP]. To confirm the presence of functional groups adsorbed on the surface of biogenic-NPs, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were employed. The outcomes demonstrated that only the use of green tea extract was successful in synthesizing zinc oxide from the zinc acetate dihydrate precursor, producing particles with an average size of approximately 25 nm. Anticancer activity and cytotoxicity of the biosynthesized Zn-GT nanoparticles were assessed against human breast cancer [MCF7] and colorectal carcinoma [HCT116] cell lines. The cytotoxicity of ZnO nanoparticles is presented with reference to normal skin [BJ1] cell line subjected to similar concentrations of the NPs. The obtained results verified a discriminative inhibition of both MCF7 and HCT116 cancer cell growth upon using Zn-GT, which completely succeeded in preventing cancer cell growth.

Antimicrobial, antioxidant, cytotoxicity and photocatalytic performance of Co doped ZnO nanoparticles biosynthesized using Annona Muricata leaf extract.

In the present study, ZnO nanoparticles doped with 3%, 5% and 7% of cobalt have been synthesized by green method using Annona muricata leaf extract. The obtained nanopowder was characterised by XRD, FTIR, XPS, HRTEM, SAED, SEM, EDAX and UV-Visible spectroscopy techniques. XRD patterns confirm the formation of pure and Co doped ZnO nanoparticles with a hexagonal wurtzite structure with high phase purity. FTIR spectra indicate the stretching vibration of Zn-O at 495cm-1. The incorporation of Co2+ ions into the ZnO lattice was identified by XPS analysis. EDX spectra confirm the existence of Co, Zn and O elements. The SEM and HRTEM micrographs show morphology of nanoparticles. The optical study specifies a decrease in energy band gap with an increase in Co-doping concentration. The photocatalytic performance of ZnO and Zn0.93Co0.07O has been examined for the degradation of methylene blue (MB) under sunlight irradiation. The antimicrobial activity of synthesized nanoparticles against s.aureus, p.aeruginosa, b.subtilis bacterial strains c.albicans and a.niger fungal strains as investigated. The Zn0.93Co0.07O nanoparticles exhibit good antioxidant properties. Moreover, the cytotoxicity of ZnO nanoparticles was evaluated against L929 normal fibroblast cells. So, this work suggests that Annona muricata leaf extract mediated pure and Co-doped ZnO nanoparticles are a potential candidate for biomedical and photocatalytic applications.

Quantifying uncertainty in dose–response screenings of nanoparticles: a Bayesian data analysis

Fitting theoretical models to experimental data for dose–response screenings of nanoparticles yields values of several hazard metrics that can support risk management. In this paper, we describe a Bayesian approach to the analysis of dose–response data for nanoparticles that takes into account multiple sources of uncertainty. Specifically, we develop a Bayesian model for the analysis of data for the cytotoxicity of ZnO nanoparticles that follow the log-logistic equation. This model reproduces the unequal variance across doses observed in the experimental data, incorporates information about the sensitivity of the cytotoxicity assay used (i.e. resazurin), and complements experimental data with historical information about the system. The model determines probability distributions for multiple values of toxicity potency (EC50), and exponential decay (the slope s); these distributions provide a direct measure of uncertainty in terms of probabilistic credibility intervals. By substituting these distributions in the log-logistic equation, we determine upper and lower limits of the benchmark dose (BMD), corresponding to upper and lower limits of credibility intervals with 95% probability given the experimental data, multiple sources of uncertainty, and historical information. In view of a reduction of costs and time of dose–response screenings, we use the Bayesian model for the cytotoxicity of ZnO nanoparticles to identify the experimental design that uses the minimum number of data while reducing uncertainty in the estimation of both fitting parameters and BMD.

Synthesis and Characterization of Zinc Oxide Nanoparticles of Solanum nigrum and Its Anticancer Activity via the Induction of Apoptosis in Cervical Cancer.

Effective cancer therapy can be achieved by using nano-drug delivery systems which provide a targeted drug delivery strategy by overcoming the drawbacks of conventional treatments like chemotherapy and radiation. ZnO nanoparticles are a potent anticancer agent that causes tumor cell destruction with the targeted drug delivery. In this present study, green synthesis of ZnO nanoparticles has been done using the plant Solanum nigrum. The synthesized ZnO nanoparticles were studied by the characterization techniques like UV-visible spectroscopy, SEM, TEM, DLS, zeta potential, FTIR, and XRD. The synthesized ZnO nanoparticles of Solanum nigrum exhibited a significant anticancer activity against HeLa cell lines through the apoptotic pathway. The cytotoxicity of ZnO nanoparticles was assessed using MTT assay, wound healing assay, DAPI staining, and acridine orange and ethidium bromide double staining. The expression patterns of β-catenin, p53, caspase-3, and caspase-9 were analyzed using reverse transcriptase-PCR. The results obtained from the study indicate that the ZnO nanoparticles of Solanum nigrum possess a dose-dependent cytotoxic effect against HeLa cell lines through the inhibition of β-catenin and increasing the levels of p53, caspase-3, and caspase-9.

Toxicity of combined exposure of ZnO nanoparticles (NPs) and myricetin to Caco-2 cells: changes of NP colloidal aspects, NP internalization and the apoptosis-endoplasmic reticulum stress pathway.

Phytochemicals as typical food components may significantly influence the toxicity of nanoparticles (NPs) in intestinal cells, indicating a need to evaluate the toxicological effects of NPs in a complex situation. Previous studies suggested that the anti-oxidative properties of phytochemicals were important to elicit cytoprotective effects against NP exposure. However, we recently found that the changes of signaling pathways may be more important for cytoprotective effects of phytochemicals. In this study, we investigated the influence of myricetin (MY) on the cytotoxicity of ZnO NPs in Caco-2 cells and the possible mechanism. MY at 50 μM showed minimal impact on the solubility and colloidal aspects of ZnO NPs, but protected Caco-2 cells from NP exposure as it increased the EC50 value. For comparison, dihydromyricetin (DMY; chemical analog of MY) increased the EC50 value to a much lesser extent. Exposure to ZnO NPs significantly induced intracellular Zn ions, whereas MY or DMY did not significantly influence the internalization of NPs. However, ZnO NPs significantly promoted the ratio of caspase-3/pro-caspase-3, which was inhibited by the presence of MY. Exposure to ZnO NPs did not significantly promote the biomarkers of endoplasmic reticulum (ER) stress, but co-exposure to ZnO NPs and MY significantly lowered the levels of a panel of ER stress biomarkers. In conclusion, these results suggested that MY could protect Caco-2 cells from ZnO NP exposure, which may not be related to the changes of colloidal stability or internalization of NPs but could be alternatively related to the reduction of ER stress leading to lower cleaved caspase-3.

First report on the mutagenicity and cytotoxicity of Zno nanoparticles in reptiles

Understanding how human activities affect animal biodiversity is essential to investigations about the biological effects of several pollutants and contaminants dispersed in the environment. This is the case of zinc oxide nanoparticles (ZnO NPs), which are emerging pollutants whose effect on reptiles’ health is completely unknown. Thus, the objective of the present study is to evaluate the possible damages induced by these NPs in Podocnemis expansa juveniles (Amazon turtle) by using morphological changes of circulating erythrocytes as nuclear toxicity biomarker. The animals were exposed to the intramuscular administration of 440 μg/kg and 440,000 μg/kg of ZnO NPs, for 10 consecutive days. The micronuclei assay and other nuclear abnormalities were performed at the end of the experiment, as well as different morphometric measurements applied to the erythrocytes. Based on the current data, ZnO NPs induced nuclear abnormalities such as micronuclei and binucleation, which are associated with carcinogenic processes and with flaws in the mitotic machinery. The low “nuclear area: erythrocyte area” ratio and larger cytoplasmic area observed for animals exposed to NPs evidenced erythrocytic change induction likely related to negative energy balance/metabolism interferences and/or to oxygen transportation efficiency by erythrocytes. This is the first report on the mutagenic and cytotoxic effect induced by NPs on representatives of a group of reptiles. This outcome suggests that further investigations must focus on better understanding the (eco)toxicological potential of ZnO NPs.

Effect of ZnO Nanoparticles on Human Bone Marrow Mesenchymal Stem Cells: Viability, Morphology, Particles Uptake, Cell Cycle and Metabolites

Despite the growing interest in nanoparticles (NPs), the evaluation of their safety use has to be deeply considered, but standardized procedures for the evaluation of their toxicity have not been defined. In vitro methods are ideal in toxicology research because they can rapidly provide reproducible results while preventing the use of animals. Primary cells are considered a better option as model systems for predicting toxicological behavior, although several cell types do not survive enough in culture and isolated cells can have substantial variability when obtained from different donors. Recently, a new test for acute toxicity based on the use of human bone marrow mesenchymal stem cells (hBMMSCs) has been developed and successfully tested in our laboratory following the ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) guidelines [1]. Along these lines, the aim of this study is to evaluate the acute cytotoxicity of ZnO nanoparticles using the new toxicity test based on hBMMSCs, while comparing their behavior with respect to the toxicity of ZnO micrometer ones. For this reason, we assessed the citotoxicity by performing Neutral Red assay, the cellular uptake by transmission electron microscopy and the effects on hBMMSCs cycle by FACS analysis. Furthermore, we also analyzed by means of GC-MS the polar metabolite profile of hBMMSCs samples treated with ZnO micro- and nanoparticles. Our results show that despite the slight differences in terms of cytotoxicity, nano and microparticles show a very different behavior with respect to their effects on hBMMSCs cycle, metabolite profile and cellular uptake.

Study of structural, morphological, optical and biomedical properties of pH based ZnO nanostructures

Nano ZnO has been synthesized at different pH values using chemical precipitation technique. The X-ray diffraction pattern shows the hexagonal wurtzite phase of ZnO nanoparticles. The crystallite size is found to decrease with increasing the pH value. From FE-SEM analysis, it can understand with increasing the pH value from 8 to 12, the morphology of ZnO nanoparticles changed from hexagonal faceted structure to nanospheroid structure. The HRTEM images are in well accordance with the FE-SEM images. The average particle size of nanospheroid morphology is 31.1 nm. The SAED pattern confirms the crystalline nature with multifaceted growth of the samples. EDAX spectrum of ZnO nanoparticles at different pH values confirms the formation of Zn and O. The absorption spectrum of ZnO nanoparticles shows that the absorbance band is slightly shifted towards the lower wavelength with increasing the pH value. The band gap energy values (by Tauc plot relation) of the ZnO nanoparticles are found in the range of 3.0–3.03eV. FTIR spectra revealed the presence of the characteristic stretching vibrational band of Zn-O bonding at 445–418 cm−1 and this is shifted to lower frequency with increasing the pH value from 8 to 12. PL spectra of ZnO nanoparticles at various pH values exhibit a strong UV emission band and green emission band. The most intense green emission band is obtained for ZnO nanoparticles at pH12. The synthesized nanoparticles show potential antibacterial activity against Gram-positive (B. subtilis and S. aureus) and Gram-negative bacteria (P. auregenia and K. Pneumonia). The cytotoxicity of ZnO nanoparticles at pH12 was evaluated against Normal (L929) and Breast cancer cell line (MB231).

Cytotoxicity of Au, ZnO and SiO2 NPs using in vitro assays with mussel hemocytes and gill cells: Relevance of size, shape and additives

Metal-bearing nanoparticles (NPs) possess unique physico-chemical characteristics that make them useful for an increasing number of industrial products and applications, but could also confer them a higher toxicity due to their higher reactivity compared to bulk forms of the same materials. There is a considerable interest in the use of in vitro techniques in environmentally relevant species, such as marine mussels, to evaluate NPs toxicity. In the present work, mussel hemocytes and gill cells were used to assess the potential toxic effects of Au, ZnO and SiO2 NPs with different sizes and shapes in parallel with their respective ionic and bulk forms and additives used in the NPs preparations. Cytotoxicity (neutral red and MTT assays) was screened at a wide range of concentrations, and LC50 values were calculated. Uptake of fluorescently labeled SIO2 NPs of 27 nm by hemocytes was also investigated. Au, ZnO and SiO2 NPs were less toxic than the corresponding ionic forms but more toxic than the bulk forms. ZnO NPs were the most toxic NPs tested which could be related with their capacity to release free ions. SiO2 NPs were not taken up by hemocytes and were not toxic to either hemocytes or gill cells. Size-dependent toxicity was found for Au NPs. Shape influenced the cytotoxicity of ZnO NPs. Finally, the presence of the additives Na-citrate and Ecodis P90 contributed to the toxicity of Au and ZnO NPs, respectively. As a general conclusion, solubility appears to play a key role in NPs toxicity to mussel cells.

Tuning the Bandgap and Cytotoxicity of ZnO by Tailoring the Nanostructures

Tuning the bandgap and cytotoxicity of ZnO nanoparticles (NPs) is very important, not only for customizing their optoelectronic and biomedical applications, but also for their cytotoxicity assay and safe usage. A unique soft‐template of polyvinylpyrrolidone has been developed here to realize a rapid room‐temperature neutral synthesis of ZnO with controlled nanostructures for tuning the bandgap and cytotoxicity of ZnO. By simply changing the reagent stoichiometry and the soft‐template shape, high‐purity ZnO rods, tripods, tubes, and unique T‐like tubes with tunable size, surface composition/charge, bandgap, and cytotoxicity are obtained. It has been revealed that the ZnO bandgap can be remarkably reduced by introducing the surface nonstoichiometry; and the ZnO‐induced cytotoxicity can be tuned by the size, shape, surface charge/composition, and bandgap of ZnO NPs at different degrees. Significantly, both the photochemistry reaction and the reactive oxygen species induced by ZnO NPs are not necessary for the ZnO‐induced cytotoxicity.

Cytotoxicity of ZnO Nanoparticles Can Be Tailored by Modifying Their Surface Structure: A Green Chemistry Approach for Safer Nanomaterials.

ZnO nanoparticles (NP) are extensively used in numerous nanotechnology applications; however, they also happen to be one of the most toxic nanomaterials. This raises significant environmental and health concerns and calls for the need to develop new synthetic approaches to produce safer ZnO NP, while preserving their attractive optical, electronic, and structural properties. In this work, we demonstrate that the cytotoxicity of ZnO NP can be tailored by modifying their surface-bound chemical groups, while maintaining the core ZnO structure and related properties. Two equally sized (9.26 ± 0.11 nm) ZnO NP samples were synthesized from the same zinc acetate precursor using a forced hydrolysis process, and their surface chemical structures were modified by using different reaction solvents. X-ray diffraction and optical studies showed that the lattice parameters, optical properties, and band gap (3.44 eV) of the two ZnO NP samples were similar. However, FTIR spectroscopy showed significant differences in the surface structures and surface-bound chemical groups. This led to major differences in the zeta potential, hydrodynamic size, photocatalytic rate constant, and more importantly, their cytotoxic effects on Hut-78 cancer cells. The ZnO NP sample with the higher zeta potential and catalytic activity displayed a 1.5-fold stronger cytotoxic effect on cancer cells. These results suggest that by modifying the synthesis parameters/conditions and the surface chemical structures of the nanocrystals, their surface charge density, catalytic activity, and cytotoxicity can be tailored. This provides a green chemistry approach to produce safer ZnO NP.

Cytotoxicity of Zinc Oxide Nanoparticles: Importance of Microenvironment

While ZnO particles are widely used in many fields, including personal care products, the high toxicity of ZnO nanoparticles has been reported and aroused great health concerns. In this study, the cytotoxicity of ZnO nanoparticles was evaluated and, in particular, the role of microenvironment in their toxicity was investigated. Our results show that ZnO nanoparticles are highly toxic to NIH/3T3 cells, inducing viability loss, membrane leakage and morphology changes. The microenviroment, here the CO2 atmosphere under cell culture condition, promoted the solubilization of ZnO nanoparticles. Then the released Zn from ZnO nanoparticles induces the cytotoxicity. The importance of microenvironment on the ZnO nanotoxicity is presented and the implications to future nanotoxicology studies are discussed.

Role of the dissolved zinc ion and reactive oxygen species in cytotoxicity of ZnO nanoparticles

With large-scale production and wide application of nanoscale ZnO, its health hazard has attracted extensive worldwide attention. In this study, cytotoxicity of different sized and shaped ZnO nanoparticles in mouse macrophage Ana-1 was investigated. And contribution of dissolved Zn 2+ and ROS in toxicity of ZnO particles was analyzed. The results indicated that ZnO particles manifested dose-dependent toxic effect on Ana-1 cells without size-dependence, and the particles shape may impact cytotoxicity of ZnO particles. When the concentration of dissolved Zn 2+ tended to equilibrium in the complete cell medium, the zinc ion concentration was approximately 10 μg/ml, inducing about 50% cell death, which was close to the cytotoxicity of ZnCl 2 (IC 50 = 13.33 μg Zn/ml). The Zn 2+ concentration had significant correlations with cell viability and LDH level induced by the supernatant of ZnO particle suspensions (incubation at 37 °C for 24 h). Thus, the dissolved Zn 2+ played the main role in toxic effect of ZnO particles. Moreover, ROS generation assays demonstrated that ZnO particles produced intrinsically a small quantity of ROS, intracellular ROS was mainly produced after ZnO particles or the dissolved Zn 2+ entered into the cells. Although intracellular ROS had significant correlations with cell viability and LDH induced by ZnO particles, intracellular ROS may not be a major factor in cytotoxicity of ZnO nanoparticles, but the cytotoxic response.