Quantitative multimodal analyses of silver nanoparticle-cell interactions: Implications for cytotoxicity

Ivask, Angela; Visnapuu, Meeri; Vallotton, Pascal; Marzouk, Ezzat R.; Lombi, Enzo; Voelcker, Nicolas H.

doi:10.1016/j.impact.2016.02.003

Cited by 21 publications

(29 citation statements)

References 30 publications

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“…Low concentrations (2 and 5 µg/mL) of AgNPs were chosen for our experiments to avoid the saturation of silver intensity on the Helios platform and to maintain adequate cellular viability (Ivask et al 2016), while still ensuring noticeable changes in cells' viability and signaling functions. Our results demonstrate that monocytes and dendritic cells had more affinity for AgNPs and were thus more vulnerable to their toxicity.…”

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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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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“…As with the analysis of fluorescent NPs, an important disadvantage to this approach is its poor quantitation power. To overcome this, some authors have introduced methods to calibrate the SSC signal of flow cytometer by parallel analysis of the samples with ICP‐MS . They demonstrated that SSC was able to reliably detect cell‐associated 10 nm Ag NPs from ~100 fg Ag per cell (translated to 10,000 NPs per cell), cell‐associated 30 nm Ag NPs from ~80 fg per cell (translated to 200 NPs per cell) and cell‐associated 70 nm Ag NPs from ~20 fg per cell (translated to five NPs per cell) (Figure (b)).…”

Section: Methods For Qualitative and Quantitative Analysis Of Cell‐asmentioning

confidence: 99%

“…For 10 nm Ag NP exposed cells, only those which Ag content was above 100 fg (10,000 10 nm particles per cell) were SSC positive; for 30 nm Ag NP exposed cells those which Ag content was above 80 fg Ag (200 30 nm NPs per cell) were SSC positive; for 70 nm Ag NP exposed cells those which Ag content was above 20 fg (5 NPs per cell) were SSC positive. Figure is based on data presented in Ivask et al (c) SSC signal of cells with 70 nm Ag particles attached to cell surface is shown on left image and SSC signal of cells with only intracellular nanoparticles is shown on right image. Exposure concentrations of Ag nanoparticles are indicated.…”

Section: Methods For Qualitative and Quantitative Analysis Of Cell‐asmentioning

confidence: 99%

Section: Methods For Qualitative and Quantitative Analysis Of Cell‐asmentioning

confidence: 99%

“…The developed etching method has also been used by other authors. For example, Ivask et al used this approach to remove Ag NPs from human T‐cells and similarly to Cho et al found that NPs with positive surface charge bound to cell surface to a greater extent than particles with negative surface charge.…”

Section: Methods To Distinguish Between Cell Surface Bound and Internmentioning

confidence: 99%

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Methodologies and approaches for the analysis of cell–nanoparticle interactions

Ivask

Mitchell

Malysheva

et al. 2017

WIREs Nanomed Nanobiotechnol

Self Cite

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How to study nanoparticle-cell interactions is the key question that puzzles researchers in the fields of nanomedicine as well as in nanotoxicology. In nanotoxicology, the amount of nanoparticles internalized by the cells or bound to the external surfaces of cells determines the toxic profile of those particles. In medical applications, cellular uptake and binding of medically effective nanoparticles decides their efficacy. Despite the importance of understanding the extent and mode of nanoparticle-cell interactions, these processes are underinvestigated, mainly due to the lack of suitable user-friendly methodologies. Here we discuss the advantages and limitations of currently available (and most advanced) microscopic, spectroscopic, and other bioanalytical methods that could be used to assess cell-nanoparticle interactions either qualitatively or quantitatively. Special emphasis is given to the methods that enable analysis and identification of nanoparticles at single-cell level, and allow intracellular localization and speciation analysis of nanoparticles. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

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Mass Cytometry and Single‐Cell RNA‐seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles

Kwon

Choi

et al. 2020

Small

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Understanding the interactions between nanoparticles (NPs) and human immune cells is necessary for justifying their utilization in consumer products and biomedical applications. However, conventional assays may be insufficient in describing the complexity and heterogeneity of cell–NP interactions. Herein, mass cytometry and single‐cell RNA‐sequencing (scRNA‐seq) are complementarily used to investigate the heterogeneous interactions between silver nanoparticles (AgNPs) and primary immune cells. Mass cytometry reveals the heterogeneous biodistribution of the positively charged polyethylenimine‐coated AgNPs in various cell types and finds that monocytes and B cells have higher association with the AgNPs than other populations. scRNA‐seq data of these two cell types demonstrate that each type has distinct responses to AgNP treatment: NRF2‐mediated oxidative stress is confined to B cells, whereas monocytes show Fcγ‐mediated phagocytosis. Besides the between‐population heterogeneity, analysis of single‐cell dose–response relationships further reveals within‐population diversity for the B cells and naïve CD4+ T cells. Distinct subsets having different levels of cellular responses with respect to their cellular AgNP doses are found. This study demonstrates that the complementary use of mass cytometry and scRNA‐seq is helpful for gaining in‐depth knowledge on the heterogeneous interactions between immune cells and NPs and can be incorporated into future toxicity assessments of nanomaterials.

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Quantitative multimodal analyses of silver nanoparticle-cell interactions: Implications for cytotoxicity

Cited by 21 publications

References 30 publications

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

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

Methodologies and approaches for the analysis of cell–nanoparticle interactions

Mass Cytometry and Single‐Cell RNA‐seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles

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