Multi-omics approaches confirm metal ions mediate the main toxicological pathways of metal-bearing nanoparticles in lung epithelial A549 cells

Dekkers, Susan; Williams, Tim D.; Zhang, Jinkang; Zhou, Jian; Vandebriel, Rob J.; Fonteyne, Liset J.J. de la; Gremmer, Eric R.; He, Shan; Guggenheim, Emily J.; Lynch, Iseult; Cassee, Flemming R.; Jong, Wim H. de; Viant, Mark R.

doi:10.1039/c8en00071a

Cited by 24 publications

(25 citation statements)

References 57 publications

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“…In our previous report, the toxicity of VO 2 to A549 cells had been systematically studied in both short‐term and long‐term exposures, and it was found that the cytotoxicity of VO 2 was mainly attributed to the dissolved species of VO 2 in the culture (Xi et al, ), similar to some other metal oxide NPs with low chemical stability (Dekkers et al, ; Wang et al, ; Yang et al, ). Measurement of the dissolved vanadium species from N‐VO 2 and T‐VO 2 in culture medium showed that the TiO 2 ‐coating could substantially reduce the dissolution of VO 2 (Figure S2).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide‐coated vanadium oxide nanoparticles to human lung cells

Tang

Liu

et al. 2019

J of Applied Toxicology

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Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO 2 NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO 2 NPs exposure through various routes. Herein, the cytotoxicity of VO 2 NPs (N-VO 2 ) and titanium dioxide-coated VO 2 NPs (T-VO 2 ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO 2 NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO 2 NPs. Under the same conditions, T-VO 2 NPs showed slightly lower cytotoxicity than N-VO 2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO 2 NPs. Titanium dioxide coating changed the surface property of VO 2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO 2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO 2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide‐coated vanadium oxide nanoparticles to human lung cells

Tang

Liu

et al. 2019

J of Applied Toxicology

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“…On the other hand, in a ROS-independent manner, AgNPs and the released Ag + ions may interact with the thiol groups of proteins, resulting in protein misfolding and eventually cell death (Riaz Ahmed et al 2017). Metal ions have also been confirmed to mediate the toxicological pathways of metal-bearing NPs in a multiomics study that involved direct infusion mass spectrometry lipidomics, polar metabolomics, and RNA-sequencing transcriptomics (Dekkers et al 2018). In this study, the majority of the molecular responses of human lung epithelial A549 cells to silver (Ag) and zinc oxide (ZnO) NPs-such as metallothionein induction, antioxidant depletion, repressed DNA repair, and apoptosis 15 induction-are similar to their responses to Ag + and Zn 2+ ions, respectively, confirming that the modes of action of these NPs are largely mediated by the corresponding dissolved metal ions.…”

Section: Discussionmentioning

confidence: 99%

Mass Cytometry Study on the Heterogeneity in Cellular Association and Cytotoxicity of Silver Nanoparticles in Human Immune Cells

Choi

Gerelkhuu

et al. 2019

Preprint

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There have been many reports about the adverse effects of nanoparticles (NPs) on the environment and human health. Conventional toxicity assessments of NPs frequently assume uniform distribution of monodisperse NPs in homogeneous cell populations, and provide information on the relationships between the administered dose of NPs and cellular responses averaged for a large number of cells. They may have limitations in describing the wide heterogeneity of cell-NP interactions, caused by cell-to-cell and NPto-NP variances. To achieve more detailed insight into the heterogeneity of cell-NP interactions, it is essential to understand the cellular association and adverse effects of NPs at single-cell level. In this study, we applied mass cytometry to investigate the interactions between silver nanoparticles (AgNPs) and primary human immune cells.High dimensionality of mass cytometry allowed us to identify various immune cell types 2 and observe the cellular association and toxicity of AgNPs in each population. Our findings showed that AgNPs had higher affinity with phagocytic cells like monocytes and dendritic cells and caused more severe toxic effects than with T cells, B cells and NK cells. Multi-element detection capability of mass cytometry also enabled us to simultaneously monitor cellular AgNP dose and intracellular signaling of individual cells, and subsequently investigate the dose-response relationships of each immune population at single-cell level, which are often hidden in conventional toxicity assays at bulk-cell level. Our study will assist future development of single-cell dose-response models for various NPs and will provide key information for the safe use of nanomaterials for biomedical applications.

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“…Metabolites can be discovered through NMR-based metabolomics by detecting characteristic spectral patterns, for example, healthy vs diseased. Principle component analysis (PCA; Figure 7D,F,H,I) and particle least squares discriminant analysis (PLS-DA; Figure 7E,G) subjected to 1D 1 H-NMR spectra of extracts from cancer cells which differentiate the clear separation between control and AgNPs [114]. A PCA represents basic discrimination.…”

Section: Pattern Recognition Of Cancer Cellsmentioning

confidence: 99%

“…The validity of the model was assessed according to cross validation results. Additionally, corresponding loading delivered several metabolic regulations by AgNPs [96,114]. The PLS-DA score plots produced by pairwise comparisons (control and AgNPs).…”

Section: Pattern Recognition Of Cancer Cellsmentioning

confidence: 99%

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Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review

Ganesan

Jang

Suh

et al. 2020

Cancers

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Silver nanoparticles (AgNPs) play significant roles in various cancer cells such as functional heterogeneity, microenvironmental differences, and reversible changes in cell properties (e.g., chemotherapy). There is a lack of targets for processes involved in tumor cellular heterogeneity, such as metabolic clampdown, cytotoxicity, and genotoxicity, which hinders microenvironmental biology. Proteogenomics and chemical metabolomics are important tools that can be used to study proteins/genes and metabolites in cells, respectively. Chemical metabolomics have many advantages over genomics, transcriptomics, and proteomics in anticancer therapy. However, recent studies with AgNPs have revealed considerable genomic and proteomic changes, particularly in genes involved in tumor suppression, apoptosis, and oxidative stress. Metabolites interact biochemically with energy storage, neurotransmitters, and antioxidant defense systems. Mechanobiological studies of AgNPs in cancer metabolomics suggest that AgNPs may be promising tools that can be exploited to develop more robust and effective adaptive anticancer therapies. Herein, we present a proof-of-concept review for AgNPs-based proteogenomics and chemical metabolomics from various tumor cells with the help of several technologies, suggesting their promising use as drug carriers for cancer therapy.

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Multi-omics approaches confirm metal ions mediate the main toxicological pathways of metal-bearing nanoparticles in lung epithelial A549 cells

Abstract: Our analyses confirm that the dissolution of metal ions mediates the main toxicological pathways of silver and zinc oxide nanoparticles.

Cited by 24 publications

References 57 publications

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide‐coated vanadium oxide nanoparticles to human lung cells

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide‐coated vanadium oxide nanoparticles to human lung cells

Mass Cytometry Study on the Heterogeneity in Cellular Association and Cytotoxicity of Silver Nanoparticles in Human Immune Cells

Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review

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