Toxicity Studies Of Nanoparticles Research Articles

Prophylactic and therapeutic role of catechin-loaded poly(D,L-lactic-co-glycolic acid) nanocapsules in gastric ulcer by in vitro and in vivo approach

Background: Gastric ulcer develops from imbalance of gastro-aggressive and protective factors. As existing drugs have adverse effects, use of natural products is in continuous expansion. In this study, we prepared nanoformulation with catechin and polylactide-co-glycolide to provide a sustained, controlled and targeted delivery. Materials & methods: Detailed characterization and toxicity study of nanoparticles were done on cells and Wistar rats. The comparative actions of free compound and nanocapsule were investigated in vitro and in vivo during treatment of gastric injury. Results: Nanocatechin improved bioavailability, reduced gastric damage at a significantly lower dose (2.5mg/kg) by safeguarding from reactive oxygen species, restored mitochondrial integrityanddownregulated MMP-9 and other inflammatory mediators. Conclusion: Nanocatechin is a better alternative for preventing and healing gastric ulcers.

Toxicity Analysis of Nano-Minimum Quantity Lubrication Machining—A Review

The lubrication properties of nanoparticles are of great interest to the manufacturing industry and led to the development of the nano-minimum quantity lubrication (NMQL) cooling strategy. To evaluate the sustainability characteristics of nano-minimum quantity lubrication, apart from analyzing the benefits of increasing machining efficiency, it is also essential to evaluate the potential detrimental effects of nanoparticles on human health and the environment. Existing literature provides substantial data on the benefits of nano-minimum quantity lubrication machining. However, the current literature does not provide researchers in the machining sector a comprehensive analysis of the toxicity of the nanoparticles used in nano-minimum quantity lubrication. This study aims to provide a comprehensive review that addresses the toxicity levels of the most frequently used nanoparticles in NMQL machining. To understand the impacts of nanoparticles on the human body and the environment, in vitro studies that evaluate the nanoparticles’ toxicity on human cells and in vitro/in vivo studies on other living organisms are considered. The results from toxicity studies on each of the chosen nanoparticles are summarized and presented in chronological order. The reviewed studies indicate transition metal dichalcogenides (MoS2 and WS2) exhibit very low toxicity when compared to other nanoparticles. The toxicity of hBN and AL2O3 nanoparticles varies depending on their lengths and crystalline structures, respectively. In conclusion, a chart that maps the toxicity levels of nanoparticles on seven different human cell lines (human lung epithelial cells (A549), human bronchial epithelial cells (Nl-20), AGS human gastric cells, human epidermal cells (HEK), human liver-derived cells (HepG2), human endothelial cells and human peripheral cells), representing exposures by inhalation, ingestion and dermal contact, was developed for easy and quick insights. This is the first attempt in open literature to combine the results of the experimental investigations of nano-minimum quantity lubrication cooling and the toxicity studies of nanoparticles, allowing researchers to make informed decisions in the selection of the most sustainable nanoparticles in the nano-minimum quantity lubrication machining process.

Concentration-dependent toxicogenomic changes of silver nanoparticles in hepatocyte-like cells derived from human induced pluripotent stem cells.

The application of silver nanoparticles (AgNPs) in consumer products has been increasing rapidly over the past decades. Therefore, in vitro models capable of accurately predicting the toxicity of AgNPs are much needed. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) represent an attractive alternative in vitro hepatotoxicity model. Yet, the use of iPSC-derived HLCs (iPSC-HLCs) for the study of nanoparticle toxicity has not been reported so far. In the present study, transcriptomic changes induced by varying concentrations (5-25 μg/ml) of AgNPs were characterized in iPSC-HLCs after 24-h exposure. AgNPs caused concentration-dependent gene expression changes in iPSC-HLCs. At all the concentrations, members of the metallothionein (MT) and the heat shock protein (HSP) families were the dominating upregulated genes, suggesting that exposure to AgNPs induced oxidative stresses in iPSC-HLCs and as a result elicited cellular protective responses in the cells. Functional analysis showed that the differentially expressed genes (DEGs) were majorly involved in the biological processes of metabolism, response to stress, and cell organization and biogenesis. Ingenuity Pathway Analysis revealed that cancer was at the top of diseases and disorders associated with the DEGs at all concentrations. These results were in accordance with those reported previously on hepatoma cell lines and primary hepatocytes. Considering the advantages iPSC-HLCs have over other liver cell models in terms of unlimited supply, consistency in quality, sustainability of function in long-term culture, and, more importantly, affordability of donor specificity, the results of the current study suggest that iPSC-HLCs may serve as a better in vitro model for liver nanotoxicology.

Toxicity Assessment of FeTiO2 and NiFe2O4 Nanoparticles on Aquatic Catfish (Siluriformes)

Background: The aquatic toxicity of Iron doped titanium dioxide nanoparticles (FeTiO2 NPs) with an average particle size of 15 nm and a Nickel ferrite nanoparticle (NiFe2O4 NPs) with an average particle size of 12 nm on catfish in water was investigated. Objective: The goal of this work is i) The synthesis and characterization of FeTiO2 NPs and NiFe2O4 NPs, ii) To prepare the different concentrations of FeTiO2 NPs and NiFe2O4 NPs, iii) Different concentrations of NPs exposure to aquatic catfish. Methods: The study was conducted with different dose rates of the NPs in the water at ambient temperature for a period of four days. During this period, abnormal behavior and mortality were observed by visual examination. The selected dose range of FeTiO2 NPs and NiFe2O4 NPs were 0.1 to 100 mg/L in water. Results: The lethal concentration for FeTiO2 NPs is > 100 mg/L and NiFe2O4 NPs were 48.6 mg/L. During the study period, abnormal behaviors such as loss of equilibrium, pigmentation, and lying down at the bottom of the aquaria were observed. Conclusion: The toxicity study of nanoparticles conducted on fish indicated that the NiFe2O4 NPs exhibited higher toxicity as compared to the FeTiO2 NPs.

Silicon-based core-shell nanoparticle's nanobiomedical characterisation

Using functionalised nanoparticles in nanobiomedical applications cause to raise questions about unintentional effect of such powerful agents on the human body. In other words, the study of nanoparticle toxicity can be considered as a curtail key for the biological applications. In this study, the core/shell nanoparticles such as Si/Au and SiO2/Au were synthesised and functionalised with some biological elements. For satisfying some medical standards and biomedical critical test conditions, a few in-vitro assays as cytotoxicity and haemolysis should be done. For this reason, cytotoxicity and haemolytic effects of the functionalised nanoparticles such as Si/Au/biotin and SiO2/Au/biotin and their derivatives were evaluated on Hep-G2 cells and humane red blood samples. It is shown that cytotoxicity and haemolysis effects of the all synthesised nanoparticles are concentration-dependent. Also, the results are shown that most cytotoxicity and haemolytic effects are observed for Si/Au and SiO2/Au without biotin groups after 48 hours and 30 minutes, respectively.

Inhalation of ZnO Nanoparticles: Splice Junction Expression and Alternative Splicing in Mice.

Despite the wide application of nanomaterials, toxicity studies of nanoparticles (NP) are often limited to in vitro cell models, and the biological impact of NP exposure in mammals has not been thoroughly investigated. Zinc oxide (ZnO) NPs are commonly used in various consumer products. To evaluate the effects of the inhalation of ZnO NP in mice, we studied splice junction expression in the lungs as a proxy to gene expression changes analysis. Female ICR mice were treated with 6.46 × 104 and 1.93 × 106 NP/cm3 for 3 days and 3 months, respectively. An analysis of differential expression and alternative splicing events in 298 targets (splice junctions) of 68 genes involved in the processes relevant to the biological effects of ZnO NP was conducted using next-generation sequencing. Three days of exposure resulted in the upregulation of IL-6 and downregulation of BID, GSR, NF-kB2, PTGS2, SLC11A2, and TXNRD1 splice junction expression; 3 months of exposure increased the expression of splice junctions in ALDH3A1, APAF1, BID, CASP3, DHCR7, GCLC, GCLM, GSR, GSS, EHHADH, FAS, HMOX-1, IFNγ, NF-kB1, NQO-1, PTGS1, PTGS2, RAD51, RIPK2, SRXN1, TRAF6, and TXNRD1. Alternative splicing of TRAF6 and TXNRD1 was induced after 3 days of exposure to 1.93 × 106 NP/cm3. In summary, we observed changes of splice junction expression in genes involved in oxidative stress, apoptosis, immune response, inflammation, and DNA repair, as well as the induction of alternative splicing in genes associated with oxidative stress and inflammation. Our data indicate the potential negative biological effects of ZnO NP inhalation.

The time-dependent cellular response mechanism upon exposure to zinc oxide nanoparticles

Zinc oxide nanoparticle is one of the nanomaterials people engaged most in their life and its health effect has been taken into concern. In this work, A549 cell line was used as cell model, and the cytotoxicity of zinc oxide nanoparticles was revealed to be concentration-dependent. Through the measurement of cellular proteome, much more differentially expressed proteins were observed after the cells being treated for 9 h than 24 h. Also, most of these proteins expressed in the pattern which showed a significant decrease after exposure to zinc oxide nanoparticles and then an increase at 24 h. Intracellular reactive oxygen species and glutathione determination indicated that high level of oxidative stress was presented in cell after treatment with zinc oxide nanoparticles for 9 h. It can be observed from western blot analysis that the expression of NF-κB p65, PNPase, and HSP90 rose significantly after 9 h of exposure. Thus, a deduction was reached that toxicity of nanoparticles consists both of particle toxicity and ion toxicity, and a long-time treatment may conceal the toxicity induced by particles. The conclusion we made highlighted the importance of exposure time in the study of nanoparticle toxicity and would provide a new perspective for studying toxicity mechanism of nanoparticles.

Biodistribution and preliminary toxicity studies of nanoparticles made of Biotransesterified β–cyclodextrins and PEGylated phospholipids

BackgroundThe modification of β-cyclodextrins (βCDs) by grafting alkyl chains on the primary and/or secondary face yields derivatives (βCD-C10) able to self-organize under nanoprecipitating conditions into nanoparticles (βCD-C10-NP) potentially useful for drug delivery. The co-nanoprecipitation of βCD-C10 with polyethylene glycol (PEG) chains yields PEGylated NPs (βCD-C10-PEG-NP) with potentially improved stealthiness. The objectives of the present study were to characterize the in vivo biodistribution of βCD-C10-PEG-NP with PEG chain length of 2000 and 5000Da using nuclear imaging, and to preliminarily evaluate the in vivo acute and extended acute toxicity of the most suitable system. Research design and methodsThe in vivo and ex vivo biodistribution features of naked and decorated nanoparticles were investigated over time following intravenous injection of 125I-radiolabeled nanoparticles to mice. The potential toxicity of PEGylated βCD-C10 nanosuspensions was evaluated in a preliminary in vivo toxicity study involving blood assays and tissue histology following repeated intraperitoneal injections of nanoparticles to healthy mice. ResultsThe results indicated that βCD-C10-PEG5000-NP presented increased stealthiness with decreased in vivo elimination and increased blood kinetics without inducing blood, kidney, spleen, and liver acute and extended acute toxicity. ConclusionsβCD-C10-PEG5000-NPs are stealth and safe systems with potential for drug delivery.

Dual flow bioreactor with ultrathin microporous TEER sensing membrane for evaluation of nanoparticle toxicity

Permeability studies across biological barriers are of primary importance in drug delivery as well as in toxicology when investigating the absorption and translocation of a substance. The study of nanomaterial interaction with epithelial barriers is of particular interest given their growing use in nanomedicine as well as concerns about their potential hazard. Here we describe the design and fabrication of a new bioreactor with an ultrathin microporous sensing support for the study of nanoparticle toxicity in intestinal epithelial cells in conditions which better recapitulate the physiological environment. Thanks to the integration of 4 electrodes in the microporous membrane, the system allows real-time and continuous sensing of TEER (trans epithelial electrical resistance) during flow without interruption or perturbation of experiments. The TEER bioreactor was tested using Caco-2 cells as an in vitro model of intestinal epithelia. When exposed to silver nanoparticles, which are known to be toxic, the embedded electrodes enabled non-invasive evaluation of barrier impairment over time. This device can be used to study barrier integrity and the kinetics of nanomaterial induced damage to epithelial barriers in physiologically relevant conditions.

Nanoparticle-Induced Membrane Pore Formation Studied with Lipid Bilayer Arrays

Nanoparticles are present environmentally as byproducts of industrial processes and in a wide range of consumer goods. Although toxicity studies of nanoparticles and other nanomaterials have only begun relatively recently, a diverse range of nanoparticles has already been shown to be toxic. Nanoparticle cytotoxicity assays provide little information about the mechanisms of nanoparticle toxicity, which are potentially complex and are not likely the same for diverse nanoparticle species. For this reason, artificial lipid bilayer platforms have begun to be used as model systems for controlled studies allowing variation of experimental parameters not possible with cellular studies, such as membrane and solution composition. Unfortunately, in some cases the low throughput characteristic of lipid bilayer experimentation can limit the experimental scope. We have recently described a lipid bilayer array platform with simultaneous bilayer formation and measurement over a 32-element array with ∼80% yield and no operator input following fluid addition.[1] The platform is modular and allows rapid cycling of the apparatus for repeated measurement. We have used this platform to measure the interactions of aminated and carboxylated polystyrene nanoparticles and a range metal oxide nanoparticle species with lipid bilayers in a wide variety of experimental conditions, including nanoparticle concentration, bilayer composition, bilayer charge, presence of serum protein, solution ionic strength, and pH. The array format permitted several thousand bilayers to be measured in total with sufficient redundancy to give statistical significance to measured results. Detailed analysis of the electrical measurements shows pore formation that is dependent on electric field, ionic strength, and nanoparticle species.1. “Lipid bilayer arrays cyclically formed and measured,” Bin Lu, Gayane Kocharyan and Jacob J. Schmidt, Biotechnology Journal 9, 446-451 (2014)

A micro-sized model for the in vivo study of nanoparticle toxicity: what has Caenorhabditis elegans taught us?

Environmental context The ability of the soil nematode Caenorhabditis elegans to withstand a wide range of environmental conditions makes it an idea model for studying the bioavailability and effects of engineered nanomaterials. We critically review what has been learned about the environmental fate of engineered nanoparticles, their effects and their mechanisms of toxicity using this model organism. Future systematic manipulation of nanoparticle properties and environmental variables should elucidate how their interaction influences toxicity and increase the predictive power of nanomaterial toxicity studies. Abstract Recent years have seen a rapid increase in studies of nanoparticle toxicity. These are intended both to reduce the chances of unexpected toxicity to humans or ecosystems, and to inform a predictive framework that would improve the ability to design nanoparticles that are less likely to cause toxicity. Nanotoxicology research has been carried out using a wide range of model systems, including microbes, cells in culture, invertebrates, vertebrates, plants and complex assemblages of species in microcosms and mesocosms. These systems offer different strengths and have also resulted in somewhat different conclusions regarding nanoparticle bioavailability and toxicity. We review the advantages offered by the model organism Caenorhabditis elegans, summarise what has been learned about uptake, distribution and effects of nanoparticles in this organism and compare and contrast these results with those obtained in other organisms, such as daphnids, earthworms, fish and mammalian models.

Iron oxide nanoparticle toxicity testing using high-throughput analysis and high-content imaging

Applying validated in vitro assays to the study of nanoparticle toxicity is a growing trend in nanomaterial risk assessment. Precise characterisation of reference nanomaterials and a well-regulated in vitro testing system are required to determine the physicochemical descriptors which dictate the toxic potential of nanoparticles. The use of automated, high-throughput technologies to facilitate the identification and prioritisation of nanomaterials which could pose a risk is desirable and developments are underway. In this study, two mammalian fibroblast lines (Balb/c 3T3 and COS-1 cells) were treated with a range of concentrations of iron oxide nanomaterials manufactured for use in medical diagnostics, using an automated platform and high-content-imaging endpoints for cell viability, oxidative stress and DNA damage (double-strand breaks). At the same time, the high-throughput comet assay was employed to measure DNA strand breaks and oxidised bases. Our results show that these methods provide a fast way to determine the toxicity of coated and uncoated iron oxide nanoparticles and, furthermore, to predict the mechanism of toxicity in vitro.

Assessing Nanoparticle Toxicity

Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cells

The production of man-made nanoparticles for various modern applications has increased exponentially in recent years, but the potential health effects of most nanoparticles are not well characterized. Unfortunately, in vitro nanoparticle toxicity studies are extremely limited by yet unresolved problems relating to dosimetry. In the present study, we systematically characterized manganese (Mn) nanoparticle sizes and examined the nanoparticle-induced oxidative signaling in dopaminergic neuronal cells. Differential interference contrast (DIC) microscopy and transmission electron microscopy (TEM) studies revealed that Mn nanoparticles range in size from single nanoparticles (~ 25 nM) to larger agglomerates when in treatment media. Manganese nanoparticles were effectively internalized in N27 dopaminergic neuronal cells, and they induced a time-dependent upregulation of the transporter protein transferrin. Exposure to 25–400 μg/mL Mn nanoparticles induced cell death in a time- and dose-dependent manner. Mn nanoparticles also significantly increased ROS, accompanied by a caspase-mediated proteolytic cleavage of proapoptotic protein kinase Cδ (PKCδ), as well as activation loop phosphorylation. Blocking Mn nanoparticle-induced ROS failed to protect against the neurotoxic effects, suggesting the involvement of other pathways. Further mechanistic studies revealed changes in Beclin 1 and LC3, indicating that Mn nanoparticles induce autophagy. Primary mesencephalic neuron exposure to Mn nanoparticles induced loss of TH positive dopaminergic neurons and neuronal processes. Collectively, our results suggest that Mn nanoparticles effectively enter dopaminergic neuronal cells and exert neurotoxic effects by activating an apoptotic signaling pathway and autophagy, emphasizing the need for assessing possible health risks associated with an increased use of Mn nanoparticles in modern applications.

Experimental considerations on the cytotoxicity of nanoparticles.

Engineered nanoparticles are one of the leading nanomaterials currently under investigation due to their applicability in various fields, including drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Moreover, the number of commercial products containing nanoparticles released on the market is rapidly increasing. Nanoparticles are already widely distributed in air, cosmetics, medicines and even in food. Therefore, the unintended adverse effect of nanoparticle exposure is a growing concern both academically and socially. In this context, the toxicity of nanoparticles has been extensively studied; however, several challenges are encountered due to the lack of standardized protocols. In order to improve the experimental conditions of nanoparticle toxicity studies, serious consideration is critical to obtain reliable and realistic data. The cell type must be selected considering the introduction route and target organ of the nanoparticle. In addition, the nanoparticle dose must reflect the realistic concentration of nanoparticles and must be loaded as a well-dispersed form to observe the accurate size- and shape-dependent effect. In deciding the cytotoxicity assay method, it is important to choose the appropriate method that could measure the toxicity of interest without the false-negative or -positive misinterpretation of the toxicity result.

How to assess cytotoxicity of (iron oxide‐based) nanoparticles. A technical note using cationic magnetoliposomes

The range of different types of nanoparticles and their biomedical applications is rapidly growing, creating a need to thoroughly examine the effects these particles have on biological entities. One of the most commonly used nanoparticle types is iron oxide nanoparticles, which can be used as MRI contrast agents. The main research topic is the in vitro labeling of cells with iron oxide nanoparticles to render the cells detectable for MRI upon in vivo transplantation. For the correct evaluation of cell function and behavior in vivo, any effects of the nanoparticles on the cells must be completely ruled out. The present work provides a technical note where a detailed overview is given of several assays that could be useful to determine nanoparticle toxicity. The assays described focus on (i) nanoparticle internalization, (ii) immediate cell toxicity, (iii) cell proliferation, (iv) cell morphology, (v) cell functionality and (vi) cell physiology. Potential pitfalls, appropriate controls and advantages/disadvantages of the different assays are given. The main focus of this work is to provide a detailed guide to help other researchers in the field interested in setting up nanoparticle-toxicity studies.

Research Highlights

Research Highlights

Nanoparticle aerosol generation methods from bulk powders for inhalation exposure studies

Inhalation toxicity studies of nanoparticles require production of test aerosols with a number of acceptable characteristics. Five different generation methods for producing a nanoparticle aerosol from the bulk powder were evaluated with the goal of producing an acceptable aerosol that is homogenous, has a consistent concentration over time in which the magnitude may be intentionally varied, and has a size distribution that is both unimodal and has a small geometric mean diameter relative to the primary particle size of the nanoparticle bulk powder. Four types of bulk powders were evaluated including titanium dioxide, silicon dioxide, polymer-coated silver, and single walled carbon nanotubes. A nebulizer was the only tested method able to produce a consistent aerosol of sufficient magnitude. However, the resulting aerosol contains particles derived from the carrier water. Prior sonication of the nanoparticle suspension alone was found to be not useful for deagglomerating nanoparticles.

The importance of physical and chemical characterization in nanoparticle toxicity studies

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