Surface modifications of ZnO nanoparticles and their cytotoxicity

ZnO is a well-known UV absorber. At small particle sizes its absorption efficiency is substantially increased and this property, combined with transparency to visible light, has attracted growing interest in its applications in personal care products such as sunscreens. However, some recent studies suggest that ZnO nanoparticles could induce considerable toxicity to certain cells and microorganisms. Aiming to reduce cytotoxicity of ZnO nanoparticles without impairing their unique properties, this paper examines the influence of surface modifications to ZnO nanoparticles using coatings such as silica (SiO2) and Poly methyl Acrylic Acid (PMAA). It was found that both PMAA and SiO2 coatings were physically attached to the ZnO surface and their presence did not weaken UV absorption of the original nanoparticles. Uncoated ZnO and SiO2-coated ZnO exhibited similar cytotoxicity to human lymphoblastoid cells, while PMAA-coated ZnO nanoparticles had little adverse effect except at high concentrations. The type of coating was also shown to affect the generation of Reactive Oxygen Species (ROS). The correlation between cell viability and ROS level led to conclusions that enhanced oxidative stress could be one of the reasons for cytotoxicity of ZnO nanoparticles.     

Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells ( approximately 28-35x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.     

In vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake

Safety and toxic effects of nanoparticles are still largely unexplored due to the multiple aspects that influence their behaviour toward biological systems. Here, we focus the attention on 12 nm spherical gold nanoparticle coated or not with hyaluronic acid compared to its precursor counterpart salt. Results ranging from the effects of a 10-days exposure in an in vitro model with BALB/c 3T3 fibroblast cells show how 12 nm spherical gold nanoparticles are internalized from 3T3 cells by endo-lysosomal pathway by an indirect measurement technique; and how gold nanoparticles, though not being a severe cytotoxicant, induce DNA damage probably through an indirect mechanism due to oxidative stress. While coating them with hyaluronic acid reduces gold nanoparticles cytotoxicity and slows their cell internalization. These results will be of great interest to medicine, since they indicate that gold nanoparticles (with or without coating) are suitable for therapeutic applications due to their tunable cell uptake and low toxicity.     

Role of size scale of ZnO nanoparticles and microparticles on toxicity toward bacteria and osteoblast cancer cells

The specific role of size scale, surface capping, and aspect ratio of zinc oxide (ZnO) particles on toxicity toward prokaryotic and eukaryotic cells was investigated. ZnO nano and microparticles of controlled size and morphology were synthesized by wet chemical methods. Cytotoxicity toward mammalian cells was studied using a human osteoblast cancer cell line and antibacterial activity using Gram-negative bacteria (Escherichia coli) as well as using Gram-positive bacteria (Staphylococcus aureus). Scanning electron microscopy (SEM) was conducted to characterize any visual features of the biocidal action of ZnO. We observed that antibacterial activity increased with reduction in particle size. Toxicity toward the human cancer cell line was considerably higher than previously observed by other researchers on the corresponding primary cells, suggesting selective toxicity of the ZnO to cancer cells. Surface capping was also found to profoundly influence the toxicity of ZnO nanoparticles toward the cancer cell line, with the toxicity of starch-capped ZnO being the lowest. Our results are found to be consistent with a membrane-related mechanism for nanoparticle toxicity toward microbes.     

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.     

Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes

Zinc oxide (ZnO) nanoparticles are widely used in cosmetics and sunscreens. Human epidermal keratinocytes may serve as the first portal of entry for these nanoparticles either directly through topically applied cosmetics or indirectly through any breaches in the skin integrity. Therefore, the objective of the present study was to assess the biological interactions of ZnO nanoparticles in primary human epidermal keratinocytes (HEK) as they are the most abundant cell type in the human epidermis. Cellular uptake of nanoparticles was investigated by scanning electron microscopy using back scattered electrons imaging as well as transmission electron microscopy. The electron microscopy revealed the internalization of ZnO nanoparticles in primary HEK after 6 h exposure at 14 microg/ml concentration. ZnO nanoparticles exhibited a time (6-24 h) as well as concentration (8-20 microg/ml) dependent inhibition of mitochondrial activity as evident by the MTT assay. A significant (p < 0.05) induction in DNA damage was observed in cells exposed to ZnO nanoparticles for 6 h at 8 and 14 microg/ml concentrations compared to control as evident in the Comet assay. This is the first study providing information on biological interactions of ZnO nanoparticles with primary human epidermal keratinocytes. Our findings demonstrate that ZnO nanoparticles are internalized by the human epidermal keratinocytes and elicit a cytotoxic and genotoxic response. Therefore, caution should be taken while using consumer products containing nanoparticles as any perturbation in the skin barrier could expose the underlying cells to nanoparticles.     

ZIF-8衍生La掺杂ZnO纳米颗粒的制备及其气敏性能

以ZIF-8及La掺杂ZIF-8为前驱体,经高温煅烧制备ZnO及La掺杂ZnO纳米颗粒.研究了La掺杂对ZnO纳米颗粒的形貌、晶体结构及气敏性能的影响.利用X射线衍射仪、扫描电子显微镜对材料的微结构进行表征,结果表明:La掺杂有利于获得更小粒径的类球形纳米结构,但La掺杂未改变ZIF-8及衍生ZnO纳米结构的晶体结构....     

Room temperature ferromagnetism in Tb-doped ZnO dilute magnetic semiconducting nanoparticles

Pure and Tb-doped ZnO nanoparticles have been synthesized by chemical co-precipitation method. The transmission electron microscopy study reveals the spherical morphology of synthesized nanoparticles with average particle size 14–18 nm. The effect of Tb-doping on structural, optical and magnetic properties has been studied. X-ray diffraction shows that pure and Tb-ZnO nanoparticles exhibit wurtzite structure having hexagonal phase with primitive unit cell. It further reveals that there is no effect of Tb-doping on the X-ray diffraction pattern up to 2 % doping, however, higher doping concentration result in accumulation of Tb on ZnO surface. Photoluminescence spectra reveal that the doping Tb in ZnO changes crystallographic structure generating non-radiative oxygen vacancies. Three emission peaks located around 423, 485 and 515 nm has been observed. Pure ZnO nanoparticles show diamagnetic character, however, Tb-doped ZnO nanoparticles exhibit room temperature ferromagnetism. The correlation between defects generated upon Tb-doping to the observed ferromagnetism, in the synthesized nanoparticles, has been reported.     

Cytotoxicity of versatile nano-micro-particles based on hierarchical flower-like ZnO

ZnO (nano)structures remain of great interest in biomedical applications due to their unique properties and possible morphologies. Biocompatibility of typically fabricated ZnO structures remains questionable and they still lack desired biological functions, whence their functionalization is of high interest. In this work, we fabricated micro-sized ZnO hierarchical flower-like structures using facile template-free hydrothermal method to act as carriers for the delivery of gold nanoparticles (Au) and/or Biotin (Vitamin B) to cells. Au nanoparticles (~24 nm), as well as Biotin molecules were successfully deposited on the ZnO surface due to non-covalent physical interactions. We have then cultured two cells lines: SH-SY5Y (human malignant neural) and HEK-293 (human non-malignant) and observed that ZnO hierarchical particles exhibited cell line-dependent cytotoxicity. It appeared that further functionalization of ZnO with Au nanoparticles and subsequently with Biotin led to lower discrepancy between the two cell lines response indicating that cytotoxic pathways of pure ZnO were masked by the available surface adsorbed particles (Au/Biotin). Two-photon immunocytochemistry microscopy further confirmed that Biotin decorated particles affected neuroblastoma cells cytoskeleton. These findings contribute to the understanding of cytotoxic pathways of surface-decorated nano-micro-structures made from ZnO with two molecules typically used in anticancer and regenerative medicine therapies.     

Effect of the surface texture and crystallinity of ZnO nanoparticles on their toxicity

We have investigated the correlation between the structural properties of ZnO nanoparticles (NPs) and their toxicity to mesenchymal stem cells (C2C12 cell line) and macrophage-derived cells (RAW 264.7 cell line). Nanopowders of grain size ranging between 5 nm and 50 nm were prepared by chemical route. Their structural properties were characterized extensively by X-ray Diffraction (XRD) and High Resolution Transmission Electron Microscopy (HRTEM). The XRD spectra showed that 50 nm sized NPs are well crystallized and present a preferential orientation along the direction normal to the (001) plane while the HREM observations revealed that most of the large size (50 nm) crystallized nanoparticles have polygonal shape which is consistent with a texture of along [001] direction. The toxicity tests showed that [001] large textured NPs have higher toxicity to inflammatory cells than nanoparticles of low crystallinity and much smaller size (5 nm). In addition, NPs have cytotoxic effects on inflammatory cells at concentration as low as 0.05 mM while ten times higher concentrations did not have significant cytotoxic effects on cells representing mesenchymal tissues. These observations are explained by the enhanced generation of Reactive Oxygen Species (ROS) at the (0001) polar surface of ZnO NP. These results provide a direct evidence of the correlation between the toxicity and the surface texture of the oxide nanoparticles. Similar correlation has been reported for the photocatalytic properties of ZnO nanoparticles.     

Endosomal Escape of Polymer‐Coated Silica Nanoparticles in Endothelial Cells

Current investigations into hazardous nanoparticles (i.e., nanotoxicology) aim to understand the working mechanisms that drive toxicity. This understanding has been used to predict the biological impact of the nanocarriers as a function of their synthesis, material composition, and physicochemical characteristics. It is particularly critical to characterize the events that immediately follow cell stress resulting from nanoparticle internalization. While reactive oxygen species and activation of autophagy are universally recognized as mechanisms of nanotoxicity, the progression of these phenomena during cell recovery has yet to be comprehensively evaluated. Herein, primary human endothelial cells are exposed to controlled concentrations of polymer‐functionalized silica nanoparticles to induce lysosomal damage and achieve cytosolic delivery. In this model, the recovery of cell functions lost following endosomal escape is primarily represented by changes in cell distribution and the subsequent partitioning of particles into dividing cells. Furthermore, multilamellar bodies are found to accumulate around the particles, demonstrating progressive endosomal escape. This work provides a set of biological parameters that can be used to assess cell stress related to nanoparticle exposure and the subsequent recovery of cell processes as a function of endosomal escape.     

Hardening of the nanoparticle-protein corona in metal (Au, Ag) and oxide (Fe3O4, CoO, and CeO2) nanoparticles

The surface modifications of metal and metal oxide nanoparticles with sizes ranging from 7 to 20 nm dispersed in commonly used cell culture medium supplemented with serum are investigated. All the tested nanoparticles adsorb proteins onto their surface, thereby forming a protein corona through a dynamic process evolving towards an irreversible coating (hard protein corona). Despite the fact that the studied nanomaterials have similar characteristics of hydrophobicity and surface charge, different temporal patterns of the protein corona formation are observed that can be considered a fingerprint for nanoparticle identification. Some of the biological and toxicological implications of the formation of the nanoparticle-protein corona are studied using the human monocytic cell line THP-1 exposed to cobalt oxide nanoparticles. Results show that production of reactive oxygen species is decreased if the nanoparticles are preincubated for 48 h with serum.     

Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems

We report on the toxicity of ZnO nanoparticles (NPs) to gram-negative and gram-positive bacterial systems, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and primary human immune cells. ZnO NP (~13 nm) showed complete inhibition of E. coli growth at concentrations 3.4 mM, whereas growth of S. aureus was completely inhibited for 1 mM. Parallel experiments using flow cytometry based assays clearly demonstrated that growth inhibitory properties of ZnO NP were accompanied by a corresponding loss of cell viability. Identical ZnO NP had minimal effects on primary human T cell viability at concentrations toxic to both gram-negative and gram-positive bacteria. Collectively, these experiments demonstrate selectivity in the toxic nature of ZnO NP to different bacterial systems and human T lymphocytes. Developing selective toxicity to biological systems and controlling it by NP design could lead to biomedical and antibacterial applications.     

Mechanistic Investigation of the Biological Effects of SiO2, TiO2, and ZnO Nanoparticles on Intestinal Cells

Silicon dioxide (SiO₂), titanium dioxide (TiO₂), and zinc oxide (ZnO) are currently among the most widely used nanoparticles (NPs) in the food industry. This could potentially lead to unintended exposure of the gastrointestinal tract to these NPs. This study aims to investigate the potential side‐effects of these food‐borne NPs on intestinal cells and to mechanistically understand the observed biological responses. Among the panel of tested NPs, ZnO NPs are the most toxic. Consistently in all three tested intestinal cell models, ZnO NPs invoke the most inflammatory responses from the cells and induce the highest intracellular production of reactive oxygen species (ROS). The elevated ROS levels induce significant damage to the DNA of the cells, resulting in cell‐cycle arrest and subsequently cell death. In contrast, both SiO₂ and TiO₂ NPs elicit minimum biological responses from the intestinal cells. Overall, the study showcases the varying capability of the food‐borne NPs to induce a cellular response in the intestinal cells. In addition to physicochemical differences in the NPs, the genetic landscape of the intestinal cell models governs the toxicology profile of these food‐borne NPs.     

Black phosphorus induced photo-doping for high-performance organic-silicon heterojunction photovoltaics

In conventional crystalline silicon (Si) homojunction solar cells,a strategy of doping by transporting phosphorus or boron impurities into Si is commonly used to build Ohmic contacts at rear electrodes.However,this technique involves an energy intensive,high temperature (～ 800 ℃) process and toxic doping materials.Black phosphorus (BP) is a two-dimensional,narrow bandgap semiconductor with high carrier mobility that exhibits broad light harvesting properties.Here,we place BP:zinc oxide (ZnO) composite films between Si and aluminum (Al) to improve their contact.Once the BP harvests photons with energies below 1.1 eV from the crystalline Si,the ZnO carrier concentration increases dramatically due to charge injection.This photo-induced doping results in a high carrier concentration in the ZnO film,mimicking the modulated doping technique used in semiconductor heterojunctions.We show that photo-induced carriers dramatically increase the conductivities of the BP-modified ZnO films,thus reducing the contact resistance between Si and Al.A photovoltaic power conversion efficiency of 15.2％ is achieved in organic-Si heterojunction solar cells that use a ZnO:BP layer.These findings demonstrate an effective way of improving Si/metal contact via a simple,low temperature process.     

Biomimicry 3D Gastrointestinal Spheroid Platform for the Assessment of Toxicity and Inflammatory Effects of Zinc Oxide Nanoparticles

Our current mechanistic understanding on the effects of engineered nanoparticles (NPs) on cellular physiology is derived mainly from 2D cell culture studies. However, conventional monolayer cell culture may not accurately model the mass transfer gradient that is expected in 3D tissue physiology and thus may lead to artifactual experimental conclusions. Herein, using a micropatterned agarose hydrogel platform, the effects of ZnO NPs (25 nm) on 3D colon cell spheroids of well‐defined sizes are examined. The findings show that cell dimensionality plays a critical role in governing the spatiotemporal cellular outcomes like inflammatory response and cytotoxicity in response to ZnO NPs treatment. More importantly, ZnO NPs can induce different modes of cell death in 2D and 3D cell culture systems. Interestingly, the outer few layers of cells in 3D model could only protect the inner core of cells for a limited time and periodically slough off from the spheroids surface. These findings suggest that toxicological conclusions made from 2D cell models might overestimate the toxicity of ZnO NPs. This 3D cell spheroid model can serve as a reproducible platform to better reflect the actual cell response to NPs and to study a more realistic mechanism of nanoparticle‐induced toxicity.     

Tailoring the photoluminescence of ZnO nanowires using Au nanoparticles

Rational design of hybrid nanostructures through attaching nanowires with nanoparticles is an effective route to enhance the existing functionalities or to explore new ones. We carry out a systematic investigation on the photoluminescence of ZnO nanowire-Au nanoparticle hybrid nanostructures synthesized by attaching Au nanoparticles onto ZnO nanowires. Citrate-stabilized 40?nm Au nanoparticles effectively quench the green emission and enhance the UV emission of the ZnO nanowires, which is consistent with the wavelength-dependent generation of surface plasmon. The UV/green emission intensity ratio could be reversibly and reproducibly tailored by attaching/detaching Au nanoparticles. This enhancement of UV emission diminishes if the Au nanoparticles are coated with a polymer layer. We also find that the orange-red emission of the ZnO nanowires is related to the excess oxygen on the ZnO surface, and it is also tunable via annealing and surface modifications.     

Effect of doping on structural and optical properties of ZnO nanoparticles: study of antibacterial properties

Sol-gel method was successfully used for synthesis of ZnO nanoparticles doped with 10 % Mg or Cu. The structure, morphology and optical properties of the prepared nanoparticles were studied as a function of doping content. The synthesized ZnO:(Mg/Cu) samples were characterized using XRD, TEM, FTIR and UV-Vis spectroscopy techniques. The samples show hexagonal wurtzite structure, and the phase segregation takes place for Cu doping. Optical studies revealed that Mg doping increases the energy band gap while Cu incorporation results in decrease of the band gap. The antibacterial activities of the nanoparticles were tested against Escherichia coli (Gram negative bacteria) cultures. It was found that both pure and doped ZnO nanosuspensions show good antibacterial activity which increases with copper doping, and slightly decreases with adding Mg.     

Study on CaCO3-coated ZnO nanoparticles based dye sensitized solar cell

Dye sensitized solar cells (DSSCs) have been fabricated using ZnO and CaCO₃-coated ZnO nanoparticles. The effect of CaCO₃ coating on the performance of DSSC has been investigated. CaCO₃-coated ZnO nanoparticles have been synthesized by hydrothermal method. X-ray diffraction patterns of synthesized nanoparticles reveal that the ZnO and CaCO₃-coated ZnO nanoparticles have respectively wurtzite and rhomb-centred structure and both having hexagonal phase. Transmission electron microscopy study reveal that ZnO and CaCO₃-coated ZnO nanoparticles possess spherical symmetry and have average particle size respectively 6.2 and 6.7 nm. In case of CaCO₃/ZnO nanoparticles, the quenching in photoluminescence emission intensity has been attributed to the decrease in recombination rate of photo-generated electron–hole pairs. UV–Vis absorption spectra, confirms that the electrodes fabricated from the CaCO₃-coated ZnO nanoparticles have higher absorbance that shows their higher dye adsorbing power. The use of CaCO₃ coating has been found to enhance the efficiency of DSSC by over 100 %.     

Facile Synthesis as well as Structural,Raman, Dielectric and Antibacterial Characteristics of Cu Doped ZnO Nanoparticles

Here, undoped and Cu doped ZnO nanoparticles(NPs) have been prepared by chemical co-precipitation technique. X-ray diffraction(XRD) results reveal that Cu ions are successfully doped into ZnO matrix without altering its wurtzite phase. The single wurtzite phase of ZnO is retained even for 10 wt% Cu doped ZnO sample. It is observed from the electron microscopy results that higher level of Cu doping varies the morphology of ZnO NPs from spherical to flat NPs. Moreover, the particle size is found to increase with the increase in Cu doping level. Raman spectroscopy results further confirm that Cu dopant has not altered the wurtzite structure of ZnO. Impedance spectroscopy results reveal that the dielectric constant and dielectric loss have increasing trend with Cu doping. Cu doping has been found to slightly decrease the bactericidal potency of ZnO nanoparticles.