In vitro comparative cytotoxicity study of aminated polystyrene,zinc oxide and silver nanoparticles on a cervical cancer cell line

Nanoparticles use in nano-biotechnology applications have increased significantly with Aminated polystyrene amine (AmPs NP), Zinc oxide (ZnO NP), and Silver (Ag NP) nanoparticles utilized in wide variety of consumer products. This has presented a number of concerns due to their increased exposure risks and associated toxicity on living systems. Changes in the structural and physicochemical properties of nanoparticles can lead to changes in biological activities. This study investigates, compares, and contrasts the potential toxicity of AmPs, ZnO and Ag NPs on an in vitro model (HeLa cells) and assesses the associated mechanism for their corresponding cytotoxicity relative to the surface material. It was noted that NPs exposure attributed to the reduction in cell viability and high-level induction of oxidative stress. All three test particles were noted to induce ROS to varying degrees which is irrespective of the attached surface group. Cell cycle analysis indicated a G2/M phase cell arrest, with the corresponding reduction in G0/G1 and S phase cells resulting in caspase-mediated apoptotic cell death. These findings suggest that all three NPs resulted in the decrease in cell viability, increase intracellular ROS production, induce cell cycle arrest at the G2/M phase and finally result in cell death by caspase-mediated apoptosis, which is irrespective of their differences in physiochemical properties and attached surface groups.     

Simple in vitro models can predict pulmonary toxicity of silver nanoparticles

To study the effects of nanomaterials after inhalation, a large number of in vitro lung models have been reported in literature. Although the in vitro models contribute to the reduction of animal studies, insufficient data exists to determine the predictive value of these in vitro models for the in vivo situation. The aim of this study was to determine the correlation between in vitro and in vivo data by comparing the dose metrics of silver nanoparticles in an in vitro lung model of increasing complexity to our previously published in vivo inhalation study. In vivo, the previously published study showed that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation. The results of the present study show that particle surface area is a suitable dose metric to describe the effects of silver nanoparticles when using a simple monolayer of lung epithelial cells. The dose metric shifted from particle surface area to particle mass when adding an increasing number of macrophages. In addition, a co-culture of endothelial cells, epithelial cells and macrophages on a Transwell® insert correlated less well to the in vivo results compared to the epithelial monolayer. We conclude that for studying the acute pulmonary toxicity of nanoparticles simple in vitro models using an epithelial monolayer better predict the in vivo response compared to complex co-culture models.     

Species-specific toxicity of copper nanoparticles among mammalian and piscine cell lines

The four copper nanoparticles (CuNPs) with the size of 25, 50, 78 and 100 nm and one type of micron-sized particles (MPs) (～500 nm) were exposed to two mammalian (H4IIE and HepG2) and two piscine (PLHC-1 and RTH-149) cell lines to test the species-specific toxicities of CuNPs. The results showed that the morphologies, ion release and size of the particles all played an important role when investigating the toxicity. Furthermore, the authors found that the particle forms of CuNPs in suspensions highly contribute to the toxicity in all exposed cell lines whereas copper ions (Cu²⁺) only caused significant responses in mammalian cell lines, indicating the species-specific toxicity of CuNPs. This study revealed that the morphologies, ion release rate of NPs as well as the species-specific vulnerabilities of cells should all be considered when explaining and extrapolating toxicity test results among particles and among species.     

Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats

Copper oxide (CuO) nanoparticles (NPs) and copper carbonate nanoparticles (Cu₂CO₃(OH)₂ NPs have applications as antimicrobial agents and wood preservatives: an application that may lead to oral ingestion via hand to mouth transfer. Rats were exposed by oral gavage to CuO NPs and Cu₂CO₃(OH)₂ NPs for five consecutive days with doses from 1 to 512?mg/kg and 4 to 128?mg/kg per day, respectively, and toxicity was evaluated at days 6 and 26. Both CuO NPs and Cu₂CO₃(OH)₂ NPs induced changes in hematology parameters, as well as clinical chemistry markers (e.g. increased alanine aminotransferase, ALT) indicative of liver damage For CuO NPs histopathological alterations were observed in bone marrow, stomach and liver mainly consisting of an inflammatory response, ulceration, and degeneration. Cu₂CO₃(OH)₂ NPs induced morphological alterations in the stomach, liver, intestines, spleen, thymus, kidneys, and bone marrow. In spleen and thymus lymphoid, depletion was noted that warrants further immunotoxicological evaluation. The NPs showed partial dissolution in artificial simulated stomach fluids, while in intestinal conditions, the primary particles simultaneously shrank and agglomerated into large structures. This means that both copper ions and the particulate nanoforms should be considered as potential causal agents for the observed toxicity. For risk assessment, the lowest bench mark dose (BMD) was similar for both NPs for the serum liver enzyme AST (an indication of liver toxicity), being 26.2?mg/kg for CuO NPs and 30.8?mg/kg for Cu₂CO₃(OH)₂ NPs. This was surprising since the histopathology evidence demonstrates more severe organ damage for Cu₂CO₃(OH)₂ NPs than for CuO NPs.     

Biodistribution and toxicity of spherical aluminum oxide nanoparticles

With the rapid development of the nano‐industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ‐aluminum oxide hydroxide nanoparticles (γ‐AlOHNPs), γ‐ and α‐AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ‐AlONPs, followed by the α‐AlONPs and γ‐AlOHNPs. In mice, γ‐AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)‐8 were observed in the blood of mice dosed with γ‐AlOHNPs (10 mg kg^?1). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS‐2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK‐293 (kidney). The results showed γ‐AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ‐AlOHNPs, but not γ‐AlONPs or α‐AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ‐AlOHNPs compared with γ‐AlONPs and α‐AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs. Copyright © 2015 John Wiley & Sons, Ltd.     

Acute toxicity test of CuO nanoparticles using human mesenchymal stem cells

Despite the growing interest in nanoparticles (NPs), standardized procedures for the evaluation of their toxicity have not been defined. The risk of human exposure is rapidly increasing and reliable toxicity test systems are urgently needed. In vitro methods are ideal in toxicology research because they can rapidly provide reproducible results while preventing the use of animals. 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 Interagency Coordinating Committee on the Validation of Alternative Methods guidelines. Along these lines, the aim of this study is to evaluate the acute cytotoxicity of copper oxide (CuO) NPs using the new toxicity test based on hBMMSCs. Our results show that CuO NPs are much more toxic compared to micrometer ones. Specifically, CuO NP exposure exhibits a significant cytotoxicity at all the concentrations used, with an IC₅₀ value of 2.5?±?0.53?µg/ml. On the other hand, CuO microsized particle exposure exhibits a very low cytotoxicity at the same concentrations, with an IC₅₀ value of 72.13?±?16.2?µg/ml.     

In vitro toxicology of ambient particulate matter: Correlation of cellular effects with particle size and components

High concentrations of airborne particulate matter (PM) have been associated with increased rates of morbidity and mortality among exposed populations. Although certain components of PM were suggested to influence these effects, no clear‐cut correlation was determined thus far. One of the possible modes of action is the induction of oxidative stress by inhaled PM triggering inflammatory responses. Therefore, the in vitro formation of reactive oxygen species (ROS) in three cell lines in the presence of five subfractions of PM₁₀, collected in Münster, Germany was investigated. The PM components chloride, nitrate, ammonium, sulfate, 68 chemical elements, and endotoxin were quantified. The highest concentration of endotoxin was found in particles of 0.42–1.2 μm aerodynamic diameters, and therefore probably subject to long‐range transport. Intracellular ROS formation in three well established mammalian cell lines (CaCo2, human; MDCK, canine; RAW264.7, mouse) only correlated positively with particle size. The two smallest PM size fractions provoked the highest rise in ROS. However, the latter did not correlate with the concentration of any PM components investigated. The smallest PM size fractions significantly dominated the number of particles. Therefore, the particle number may be most effective in inducing oxidative stress in vitro. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.     

Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles.

Previous studies have reported little correlation between the relative toxicity of particle types when comparing lung toxicity rankings following in vivo instillation versus in vitro cell culture exposures. This study was designed to assess the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoscale particle types in rats. In the in vivo component of the study, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle types: (1) carbonyl iron (CI), (2) crystalline silica (CS) (Min-U-Sil 5, alpha-quartz), (3) precipitated amorphous silica (AS), (4) nano-sized zinc oxide (NZO), or (5) fine-sized zinc oxide (FZO). Depending on particle type and solution state, these particles range in size from 90 to 500 nm in size. Following exposures, the lungs of exposed rats were lavaged and inflammation (neutrophil recruitment) and cytotoxicity end points (bronchoalveolar lavage [BAL] fluid lactate dehydrogenase [LDH] values) were measured at 24 h, 1 week, 1 and 3 months postexposure. For the in vitro component of the study, three different culture conditions were utilized. Cultures of (1) rat L2 lung epithelial cells, (2) primary alveolar macrophages (AMs) (collected via BAL from unexposed rats), as well as (3) AM-L2 lung epithelial cell cocultures were incubated with the particle types listed above, and the culture fluids were evaluated for cytotoxicity end points (LDH, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan [MTT]) as well as inflammatory cytokines (macrophage inflammatory 2 protein [MIP-2], tumor necrosis factor alpha [TNF-alpha], and interleukin-6 [IL-6]) at one (i.e., cytokines) or several (cytotoxicity) time periods. Results of in vivo pulmonary toxicity studies demonstrated that instilled CI particles produced little toxicity. CS particles produced sustained inflammation and cytotoxicity. AS particles produced reversible and transient inflammatory responses. NZO or FZO particles produced potent but reversible inflammation which was resolved by 1 month postinstillation exposure. Results of in vitro pulmonary cytotoxicity studies demonstrated a variety of responses to the different particle types, primarily at high doses. With respect to the LDH results, L2 cells were the most sensitive and exposures to nano- or fine-sized ZnO for 4 or 24 h were more cytotoxic than exposures to CS or AS particles. Macrophages essentially were resistant and epithelial macrophage cocultures generally reflected the epithelial results at 4 and 24 h incubation, but not at 48 h incubation. MTT results were also interesting but, except for nano- and fine-sized ZnO, did not correlate well with LDH results. Results of in vitro pulmonary inflammation studies demonstrated that L2 cells did not produce MIP-2 cytokines, but CS- or AS-exposed AMs and, to a lesser degree, cocultures secreted these chemotactic factors into the culture media. Measurements of TNF-alpha in the culture media by particle-exposed cells demonstrated little activity. In addition, IL-6 secretion was measured in CS, AS, and nano-sized ZnO-exposed cocultures. When considering the range of toxicity end points to five different particle types, the comparisons of in vivo and in vitro measurements demonstrated little correlation, particularly when considering many of the variables assessed in this study-such as cell types to be utilized, culture conditions and time course of exposure, as well as measured end points. It seems clear that in vitro cellular systems will need to be further developed, standardized, and validated (relative to in vivo effects) in order to provide useful screening data on the relative toxicity of inhaled particle types.     

Toxicity profiling of water contextual zinc oxide,silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems

Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by‐products contained within the effluent of domestic and industrial run‐off. The partial recycling of water laden with ENPs, albeit at ultra‐low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water‐relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico‐predicted water‐relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1459–1469, 2015.     

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment.

Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C?×?T protocol). The dose is expressed as 6?h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2?mg/m³ CuO NPs, with a primary particle size of 10 9.2–14?nm and an MMAD of 1.5?μm.

Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4?mg/m³. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2?mg/m³. The olfactory epithelium in the nose degenerated 24?h after exposure to 6.3 and 13.2?mg/m³, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver.

Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.     

Acute toxicity of zinc oxide nanoparticles to the rat olfactory system after intranasal instillation

With the increased applications of zinc oxide (ZnO) nanoparticles (NPs), the toxicity of ZnO NPs arouses great concerns from the nano community and the general public. In this study, we report the toxicity of ZnO NPs (30 nm) to the rat olfactory system after intranasal instillation revealed by non‐invasive magnetic resonance imaging (MRI). MRI scans were performed on a 4.7‐T scanner at 1, 2, 3 and 7 days post‐exposure, and the histological changes of the rat olfactory epithelium were evaluated. The influences of chemical component and dispersant of the NPs were also investigated. In addition, an olfactory behavior test was performed. The MRI and histological results indicated that ZnO NPs induced significant damages to the olfactory epithelium, including disruption of the olfactory epithelial structures and inflammation. The destruction of mitochondria in epithelial cells was observed under transmission electron microscopy (TEM), suggesting that the possible toxicological mechanism might involve cellular energy metabolic dysfunction. Further, the lesion of the olfactory epithelium disturbed sniffing behaviors of the treated animals. The results suggest that MRI is potentially useful as a screening tool to assess the consequence of occupational exposure of ZnO NPs. Caution should therefore be taken during the use and disposal of ZnO NPs to prevent the unintended public health impacts. Copyright © 2012 John Wiley & Sons, Ltd.     

Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells

Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO₂ and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6–8?nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn⁺ ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.     

In vitro toxicological assessment of iron oxide,aluminium oxide and copper nanoparticles in prokaryotic and eukaryotic cell types

Metallic nanoparticles (NPs) have a variety of applications in different industries including pharmaceutical industry where these NPs are used mainly for image analysis and drug delivery. The increasing interest in nanotechnology is largely associated with undefined risks to the human health and to the environment. Therefore, in the present study cytotoxic and genotoxic effects of iron oxide, aluminium oxide and copper nanoparticles were evaluated using most commonly used assays i.e. Ames assay, in vitro cytotoxicity assay, micronucleus assay and comet assay. Cytotoxicity to bacterial cells was assessed in terms of colony forming units by using Escherichia coli (gram negative) and Bacillus subtilis (gram positive). Ames assay was carried out using two bacterial strains of Salmonella typhimurium TA98 and TA100. Genotoxicity of these NPs was evaluated following exposure to monkey kidney cell line, CHS-20. No cytotoxic and genotoxic effects were observed for iron oxide, and aluminium oxide NPs. Copper NPs were found mutagenic in TA98 and in TA100 and also found cytotoxic in dose dependent manner. Copper NPs induced significant (p?相似文献   

Mechanisms of toxicity associated with six tyrosine kinase inhibitors in human hepatocyte cell lines

Tyrosine kinase inhibitors have revolutionized the treatment of certain cancers. They are usually well tolerated, but can cause adverse reactions including liver injury. Currently, mechanisms of hepatotoxicity associated with tyrosine kinase inhibitors are only partially clarified. We therefore aimed at investigating the toxicity of regorafenib, sorafenib, ponatinib, crizotinib, dasatinib and pazopanib on HepG2 and partially on HepaRG cells. Regorafenib and sorafenib strongly inhibited oxidative metabolism (measured by the Seahorse‐XF24 analyzer) and glycolysis, decreased the mitochondrial membrane potential and induced apoptosis and/or necrosis of HepG2 cells at concentrations similar to steady‐state plasma concentrations in humans. In HepaRG cells, pretreatment with rifampicin decreased membrane toxicity (measured as adenylate kinase release) and dissipation of adenosine triphosphate stores, indicating that toxicity was associated mainly with the parent drugs. Ponatinib strongly impaired oxidative metabolism but only weakly glycolysis, and induced apoptosis of HepG2 cells at concentrations higher than steady‐state plasma concentrations in humans. Crizotinib and dasatinib did not significantly affect mitochondrial functions and inhibited glycolysis only weakly, but induced apoptosis of HepG2 cells. Pazopanib was associated with a weak increase in mitochondrial reactive oxygen species accumulation and inhibition of glycolysis without being cytotoxic. In conclusion, regorafenib and sorafenib are strong mitochondrial toxicants and inhibitors of glycolysis at clinically relevant concentrations. Ponatinib affects mitochondria and glycolysis at higher concentrations than reached in plasma (but possibly in liver), whereas crizotinib, dasatinib and pazopanib showed no relevant toxicity. Mitochondrial toxicity and inhibition of glycolysis most likely explain hepatotoxicity associated with regorafenib, sorafenib and possibly pazopanib, but not for the other compounds investigated.     

Cellular toxicity of hydrazine in primary rat hepatocytes.

Hydrazine (HzN) is an aircraft fuel and propellant used by the U.S. Air Force. The current study was undertaken to evaluate the acute toxicity of HzN in primary rat hepatocytes in vitro with reference to oxidative stress. The effects of short-term exposure (4 h) of hepatocytes to HzN were investigated with reference to viability, mitochondrial function, and biomarkers of oxidative stress. The viability data showed an increase in lactate dehydrogenase leakage and a decrease in mitochondrial activity with increasing concentration of HzN. The results of studies of oxidative stress biomarkers showed a depletion of reduced glutathione (GSH) and an increase in oxidized GSH, increased reactive oxygen species generation, lipid peroxidation, and reduced catalase activity. Furthermore, depletion of GSH and catalase activity in hepatocytes by buthionine sulfoximine and 3-amino triazole, respectively, prior to exposure to HzN, increased its toxicity. The results suggest that acute HzN-induced cytotoxicity in rat hepatocytes is likely to be mediated through oxidative stress.     

Male- and female-derived somatic and germ cell-specific toxicity of silver nanoparticles in mouse

Silver nanoparticles (AgNPs) are widely used as an antibiotic agent in textiles, wound dressings, medical devices, and appliances such as refrigerators and washing machines. The increasing use of AgNPs has raised concerns about their potential risks to human health. Therefore, this study was aimed to determine the impact of AgNPs in germ cell specific complications in mice. The administration of AgNPs results in toxicity in mice; however, a more detailed understanding of the effects of AgNPs on germ cells remains poorly understood. Here, we demonstrate the effects of AgNPs (20?nm in diameter) in a mouse Sertoli and granulosa cells in vitro, and in male and female mice in vivo. Soluble silver ion (Ag⁺)-treated cells were used as a positive control. We found that excessive AgNP-treated cells exhibited cytotoxicity, the formation of autophagosomes and autolysosomes in Sertoli cells. Furthermore, an increase in mitochondrial-mediated apoptosis by cytochrome c release from mitochondria due to translocation of Bax to mitochondria was observed. In in vivo studies, the expression of pro-inflammatory cytokines, including tumor necrosis factor α, interferon-γ, ?6, ?1β, and monocyte chemoattractant protein-1 were significantly increased (p?<?0.05). Histopathological analysis of AgNP-treated mice shows that a significant loss of male and female germ cells. Taken together, these data suggest that AgNPs with an average size of 20?nm have negative impact on the reproduction.     

High inflammogenic potential of rare earth oxide nanoparticles: the New Hazardous Entity

Due to the exponential increase in the development and utilization of rare earth oxide nanoparticles (REO NPs) in various fields, the possibility of exposure in humans by inhalation has increased. However, there are little information about hazards of REO NPs and its mechanisms of toxicity. In this study, we evaluated the acute pulmonary inflammation using 10 REO NPs (Dy₂O₃, Er₂O₃, Eu₂O₃, Gd₂O₃ La₂O₃, Nd₂O₃, Pr₆O₁₁, Sm₂O₃, Tb₄O₇, and Y₂O₃) and four well-known toxic particles (CuO, NiO, ZnO, and DQ12). Minimum three doses per NP were instilled into the lungs of female Wistar rats at surface area dose metric and lung inflammation was evaluated at 24?h post-instillation by bronchoalveolar lavage fluid (BALF) analysis and histopathological observation. All types of REO NPs showed common pathological changes including mild to moderate infiltration of neutrophils and activated macrophages in the alveoli, peribronchial, and perivascular region. The inflammogenic potential evaluated by the number of granulocytes divided by the treated surface area dose showed all types of REO NPs has much higher inflammogenic potential than DQ12, ZnO, and NiO NPs. The correlation plot between the number of granulocytes and the potential for reactive oxygen species (ROS) generation showed a good correlation with exception of Pr₆O₁₁. The higher inflammogenic potential of REO NPs than that of well-known highly toxic particles imply that REO NPs need special attention for inhalation exposure and more studies are needed. In addition, the potential of ROS generation is one of the key factors producing lung inflammation by REO NPs.     

Analytically monitored digestion of silver nanoparticles and their toxicity on human intestinal cells

Orally ingested nanoparticles may overcome the gastrointestinal barrier, reach the circulatory system, be distributed in the organism and cause adverse health effects. However, ingested nanoparticles have to pass through different physicochemical environments, which may alter their properties before they reach the intestinal cells. In this study, silver nanoparticles are characterised physicochemically during the course of artificial digestion to simulate the biochemical processes occurring during digestion. Their cytotoxicity on intestinal cells was investigated using the Caco-2 cell model. Using field-flow fractionation combined with dynamic light scattering and small-angle X-ray scattering, the authors found that particles only partially aggregate as a result of the digestive process. Cell viabilities were determined by means of CellTiter-Blue® assay, 4′,6-diamidino-2-phenylindole-staining and real-time impedance. These measurements reveal small differences between digested and undigested particles (1–100 µg/ml or 1–69 particles/cell). The findings suggest that silver nanoparticles may indeed overcome the gastrointestinal juices in their particulate form without forming large quantities of aggregates. Consequently, the authors presume that the particles can reach the intestinal epithelial cells after ingestion with only a slight reduction in their cytotoxic potential. The study indicates that it is important to determine the impact of body fluids on the nanoparticles of interest to provide a reliable interpretation of their nano-specific cytotoxicity testing in vivo and in vitro.     

In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe3O4‐TiO2 nanoparticles in human liver cells

Recent studies show that Janus Fe₃O₄‐TiO₂ nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe₃O₄‐TiO₂ nanoparticles, an in vitro study using a human liver cell line HL‐7702 cells was conducted. For comparison, the Janus Fe₃O₄‐TiO₂ NPs parent material TiO₂ NPs was also evaluated. Results showed that both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC‐1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO₂ NPs induced slightly higher cytotoxicity than Fe₃O₄‐TiO₂ NPs in HL7702 cells. Western blotting indicated that both TiO₂ NPs and Fe₃O₄‐TiO₂ NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe₃O₄‐TiO₂ NPs induced higher signal protein expressions than TiO₂ NPs under a high treatment dose. However, under a low dose (6.25 μg/cm²), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe₃O₄‐TiO₂ NPs.     

Amorphous silica coatings on magnetic nanoparticles enhance stability and reduce toxicity to in vitro BEAS-2B cells

Background: Nanoparticles are being rapidly assimilated into numerous research fields and consumer products. A concurrent increase in human exposure to such materials is expected. Magnetic nanoparticles (MNPs) possess unique and beneficial features, increasing their functionality and integrative potential. However, MNP toxicity characterization is limited, especially in regards to the human respiratory system. This study aimed to assess the in vitro effects of airborne MNPs on BEAS-2B cells. Uncoated iron oxide was compared with two amorphous silica-coated MNPs, hypothesizing the coatings reduced toxicity and increased particle stability.

Method: BEAS-2B cells were cultured at an air–liquid interface and exposed to airborne MNPs using a fabricated exposure device. Indices of cytotoxicity, inflammatory response, oxidative stress, and iron homeostasis were monitored postexposure via cell viability assays and qRT-PCR. Concentrations of soluble iron-associated with different MNPs were also examined before and after contact with several aqueous organic and inorganic acids.

Results: The silica-coated MNPs had reduced soluble iron concentrations. This result indicates that the silica coating provides a barrier to and prevents the mobilization of soluble iron from the particle to the cell, thereby reducing the risk of oxidative stress or alterations of iron homeostasis. Cells exposed to MagSilica50 and MagSilica50–85® showed little to no indications of cytotoxicity or induction of inflammatory response/oxidative stress at the examined delivery concentrations.

Conclusion: MNPs coated with amorphous silica are protected from acidic erosion. Correspondingly, the particle stability translates into reduced cytotoxicity and cellular influence on human airway epithelial cells.