Publications (38)201.28 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: To gain a better understanding of nanoparticle exposure in human nasal cavities, laboratory animals (e.g. rat) are used for in vivo studies. However, due to anatomical differences between human and rodent nasal cavities, direct particle deposition comparisons between species are difficult. This paper presents a comparative nanoparticle (1nm, 10nm, and 100nm) deposition study using anatomically realistic models of a human and rat nasal cavity. The particle deposition fraction was highest consistently in the main nasal passage, for all nanoparticles tested, in the human model; while this was only the case for 10nm, and 100nm particles for the rodent model, where greater deposition was found in the anterior nose for 1nm particles. A deposition intensity (DI) term was introduced to represent the accumulated deposition fraction on cross-sectional slices. A common and preferential deposition site in the human model was found for all nanoparticles occurring at a distance of 3.5cm inside the nasal passage. For the rodent model maximum DI occurred in the vestibule region at a distance of 0.3 cm, indicating that the rodent vestibule produces exceptionally high particle filtration capability. We also introduced a deposition flux which was a ratio of the regional deposition fraction relative to the region’s surface area fraction. This value allowed direct comparison of deposition flux between species, and a regional extrapolation scaling factor was found (e.g. 1/10 scale for vestibule region for rat to human comparison). This study bridges the in-vitro exposure experiments and in-vivo nanomaterials toxicity studies, and can contribute towards improving inter-species exposure extrapolation studies in the future.
- [Show abstract] [Hide abstract] ABSTRACT: Concerns have arisen about the health and environmental impacts of increasing commercial use of silver nanoparticles (AgNPs). However, the toxic mechanisms and target tissues of AgNPs have not been fully defined. In this paper, we investigated the tissue toxicity of mouse after intravenous administration of AgNPs at a single-dose of 0.2, 2 or 5 mg/kg (body weight), respectively. Biodistribution, endoplasmic reticulum stress, oxidative stress were examined in mouse organs at eight hours after exposure. Stress markers, e.g. HSP70, BIP, p-IRE1, p-PERK, chop and xbp-1s proteins/genes were significantly upregulated in a dose-dependent manner. In liver, spleen, lung and kidney, high stress accompanied with apoptosis occurrence. Low stress levels were observed in heart and brain. Thus, it is proposed that liver, spleen, lung and kidney are dominant target tissues of AgNPs exposure. The lower stress and toxicity in heart and brain were in agreement with lower AgNP accumulation. The present results demonstrated that AgNPs exposure eventually resulted in permanent toxic damage by gradually imposing stress impacts on target organs. These findings highlight the potent applications of stress markers in future risk evaluation of silver nanoparticle toxicity.
Dataset: nn5b05783 si 001
- [Show abstract] [Hide abstract] ABSTRACT: Indoor air quality has great impact on the human health. An increasing number of studies have shown that printers could release particulate matters and pose adverse effects on indoor air quality. In this study, a thorough investigation was designed to assess the aerosol printer particle total number concentration (TNC) and size distribution in normal office environment, one copy center, and a clean chamber. Particle analyzers, SMPS, OPS, and CPC3007 were used to monitor the total printing process. In normal office environment, 37 laser printers out of all surveyed 55 printers were classified as high particle emitters. Comparing to laser printers, 5 inkjet printers showed no particle emission. Particle emission level in a copy center increased slightly with TNC elevating to about 2 times of the aerosol background. Simulating test in a clean chamber indicated that printeremitted particles were dominated by particles in nanoscale (diameter of particle, Dp
- [Show abstract] [Hide abstract] ABSTRACT: Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols usually have low toxicities, making them promising agents for antitumor chemotherapeutics. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) can contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, gadolinium endohedral metallofullerenols Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application.
- [Show abstract] [Hide abstract] ABSTRACT: Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MR contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.
- [Show abstract] [Hide abstract] ABSTRACT: Monocytes/macrophages are important constituents of the innate immune system. Monocyte-macrophage differentiation is not only crucial for innate immune responses, but is also related to some cardiovascular diseases. Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials because of their broad-spectrum antimicrobial properties. However, the effect of AgNPs on the functions of blood monocytes is scarcely reported. Here, we report the impedance effect of AgNPs on THP-1 monocyte differentiation, and that this effect was mediated by autophagy blockade and lysosomal impairment. Firstly, AgNPs inhibit phorbol 12-myristate 13-acetate (PMA)-induced monocyte differentiation by down-regulating both expression of surface marker CD11b and response to lipopolysaccharide (LPS) stimulation. Secondly, autophagy is activated during PMA-induced THP-1 monocyte differentiation, and the autophagy inhibitor chloroquine (CQ) can inhibit this process. Thirdly, AgNPs block the degradation of the autophagy substrate p62 and induce autophagosome accumulation, which demonstrates the blockade of autophagic flux. Fourthly, lysosomal impairments including alkalization and decrease of lysosomal membrane stability were observed in AgNP-treated THP-1 cells. In conclusion, we demonstrate that the impedance of monocyte-macrophage differentiation by AgNPs is mediated by autophagy blockade and lysosomal dysfunction. Our results suggest that crosstalk exists in different biological effects induced by AgNPs.
- [Show abstract] [Hide abstract] ABSTRACT: Silver nanoparticles (AgNPs) attract considerable public attention both for their antimicrobial properties and their potential adverse effects. In the present study, endoplasmic reticulum (ER) stress was used as a sensitive and early biomarker to evaluate the toxic potential of AgNPs in three different human cell lines in vitro and in vivo in mice. In 16HBE cells, the activation of ER stress signaling pathway was observed by upregulated expression including xbp-1s, chop/DDIT3, TRIB3, ADM2, BIP, Caspase-12, ASNS and HERP at either the mRNA and/or protein levels. However, these changes were not observed in HUVECs or HepG2 cells. Furthermore, mice experiments showed that different tissues had various sensitivities to AgNPs following intratracheal instillation exposure. The lung, liver and kidney showed significant ER stress responses, however, only the lung and kidney exhibited apoptosis by TUNEL assay. The artery and tracheal tissues had lower ER stress and apoptosis after exposure. The lowest observable effect concentrations (LOEC) were proposed based on evaluation of AgNP induced ER stress response in cell and mouse models. In summary, preliminary evaluation of AgNP toxicity by monitoring the ER stress signaling pathway provides new insights toward the understanding the biological impacts of AgNPs. The adverse effects of exposure to AgNPs may be avoided by rational use within the safe dose. Copyright © 2015 Elsevier Ltd. All rights reserved.
Dataset: Huo-biomaterials 2015 supplement
- [Show abstract] [Hide abstract] ABSTRACT: Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry - hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO - uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques - precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially 'weak-embryotoxic' and ZnO and SiO2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO2 displayed higher toxicity compared with ZnO and SiO2. Importantly, the in vitro methodology applied could identify cell- and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects.
- [Show abstract] [Hide abstract] ABSTRACT: To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information of intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectrometry, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag0)n, to Ag+ ions and Ag-O-, then Ag-S- species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the present approach provides an integrated strategy capable of exploring the chemical origins of cytotoxicity of metallic nanoparticles.
- [Show abstract] [Hide abstract] ABSTRACT: Fullerene derivatives have attracted extensive attention in biomedical fields and polyhydroxyl fullerene (fullerenol), a water-soluble fullerene derivative, is demonstrated as a powerful antioxidant. To further assess their anti-aging and anti-stress potential, we employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the effects of fullerenol on the growth, development, behavior and anti-stress ability in vivo. The data show that fullerenol has no obviously toxic effect on nematodes and can delay C. elegans aging progress under normal condition. Further studies demonstrate that fullerenol attenuates endogenous levels of reactive oxygen species and provides protection to C. elegans under stress conditions by up-regulating stress-related genes in a DAF-16 depend manner and improving lifespan. In summary, our data suggest that fullerenol might be a safe and reasonable anti-aging candidate with great potential in vivo.
- [Show abstract] [Hide abstract] ABSTRACT: Engineered gold nanoparticles (AuNPs) have recently drawn an increased interest in disease diagnostics and therapies. However, reports on detailed studies of AuNPs regarding their pharmacodynamics, pharmacokinetics, biodistribution, metabolism and potential toxicity are limited. It is common knowledge that the in vivo behavior and fate of various AuNPs are influenced by their surface and size. However, a comprehensive description and understanding of all variables is crucial for their further development toward potential clinical use. In this article, we describe the pharmacokinetics and biodistribution of mesoporous silica-coated gold nanorods functionalized with polyethylene glycol or bovine serum albumin (AuNR@SiO2-PEG and AuNR@SiO2-BSA, respectively) in tumor-bearing balb/c mice. To gain further insight into the pharmacokinetics, biodistribution and tumor uptake, we also compare the results with BSA functionalized gold nanorods (AuNR-BSA) and gold clusters (AuNC-BSA). The results reveal that AuNR@SiO2-PEG have the longest blood half-life and the maximum percentage content in the tumor at 24 h and 3 days compared to other AuNPs. AuNR@SiO2-PEG, AuNR@SiO2-BSA and AuNR-BSA had primarily accumulated in the liver and spleen without apparent metabolism after 3 days, while the content of AuNC-BSA in the liver, spleen and kidneys showed an obvious decrease, indicating a size-dependent metabolism process. Our results demonstrate how to manipulate the size and surface chemistry of AuNPs to prolong their blood circulation time, improve delivery into target organs and achieve a safer design of nanomedicines.
- [Show abstract] [Hide abstract] ABSTRACT: With rapid development of novel nanomaterials (NMs), the state of the art technologies with high efficiency and high-throughput characteristics had been applied for nanosafety evaluation. Highcontent screening (HCS), a cell based multi-parametric image analysis technique, was adopted in the evaluation of eight different NMs in this study. A set of different endpoints including reactive oxygen species (ROS) production, Ca2+ transient, mitochondrial membrane potential (MMP) and cellular pH levels were checked in human bronchial epithelial (16HBE) cells after incubating with NMs for 24 hours. All NMs induced significant increase of intracellular ROS levels in 16HBE cells, although the decrease of cell viability was only found in Ag and ZnO NMs-treated cells. MMP level had a dose-response decrease in Ag, ZnO and CeO2 NMs-treated cells, while showed a significant increase in TiO2 NMs-treated cells. All tested NMs showed significant up-regulation of cellular lysosomal pH levels. However, none of NMs caused significant changes in cellular Ca2+ level at 24-hour time point. HCS allows for efficient and reliable screening of multiple responses of cells simultaneously within one screen test, which can avoid the problematic interpretation of investigations when carried on a single toxicological endpoint. Therefore, the present data provide insight and inspiration that HCS is an effective and powerful method for image-based assessments with a broad set of biological endpoints in toxicity evaluation of nanomaterials.
Dataset: ja511560b si 001
- [Show abstract] [Hide abstract] ABSTRACT: A number of studies have demonstrated that MWCNTs induce granuloma formation and fibrotic responses in vivo, and it has been recently reported that MWCNT-induced macrophage activation and subsequent TGF-β secretion contribute to pulmonary fibrotic responses. However, their direct effects against alveolar type-II epithelial cells and fibroblasts and the corresponding underlying mechanisms remain largely unaddressed. Here, MWCNTs are reported to be able to directly promote fibroblast-to-myofibroblast conversion and the epithelial-mesenchymal transition (EMT) through the activation of the TGF-β/Smad signaling pathway. Both of the cell transitions may play important roles in MWCNT-induced pulmonary fibrosis. Firstly, in-vivo and in-vitro data show that long MWCNTs can directly interact with fibroblasts and epithelial cells, and some of them may be uptaken into fibroblasts and epithelial cells by endocytosis. Secondly, long MWCNTs can directly activate fibroblasts and increase both the basal and TGF-β1-induced expression of the fibroblast-specific protein-1, α-smooth muscle actin, and collagen III. Finally, MWCNTs can induce the EMT through the activation of TGF-β/Smad2 signaling in alveolar type-II epithelial cells, from which some fibroblasts involved in pulmonary fibrosis are thought to originate. These observations suggest that the activation of the TGF-β/Smad2 signaling plays a critical role in the process of the fibroblast-to-myofibroblast transition and the EMT induced by MWCNTs.
Chinese Academy of SciencesPeping, Beijing, China
Technical Institute of Physics and ChemistryPeping, Beijing, China