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Cited by 326

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Use of a High-Throughput Screening Approach Coupled with In Vivo Zebrafish Embryo Screening To Develop Hazard Ranking for Engineered Nanomaterials

Open access
George, Saji, Xia, Tian, Rallo, Robert, Zhao, Yan, Ji, Zhaoxia, Lin, Sijie, Wang, Xiang, Zhang, Haiyuan, France, Bryan, Schoenfeld, David, Damoiseaux, Robert, Liu, Rong, Lin, Shuo, Bradley, Kenneth A., Cohen, Yoram, Nel, André E·2011·ACS Nano

Abstract

Because of concerns about the safety of a growing number of engineered nanomaterials (ENM), it is necessary to develop high-throughput screening and in silico data transformation tools that can speed up in vitro hazard ranking. Here, we report the use of a multiparametric, automated screening assay that incorporates sublethal and lethal cellular injury responses to perform high-throughput analysis of a batch of commercial metal/metal oxide nanoparticles (NP) with the inclusion of a quantum dot (QD1). The responses chosen for tracking cellular injury through automated epifluorescence microscopy included ROS production, intracellular calcium flux, mitochondrial depolarization, and plasma membrane permeability. The z-score transformed high volume data set was used to construct heat maps for in vitro hazard ranking as well as showing the similarity patterns of NPs and response parameters through the use of self-organizing maps (SOM). Among the materials analyzed, QD1 and nano-ZnO showed the most prominent lethality, while Pt, Ag, SiO2, Al2O3, and Au triggered sublethal effects but without cytotoxicity. In order to compare the in vitro with the in vivo response outcomes in zebrafish embryos, NPs were used to assess their impact on mortality rate, hatching rate, cardiac rate, and morphological defects. While QDs, ZnO, and Ag induced morphological abnormalities or interfered in embryo hatching, Pt and Ag exerted inhibitory effects on cardiac rate. Ag toxicity in zebrafish differed from the in vitro results, which is congruent with this material's designation as extremely dangerous in the environment. Interestingly, while toxicity in the initially selected QD formulation was due to a solvent (toluene), supplementary testing of additional QDs selections yielded in vitro hazard profiling that reflect the release of chalcogenides. In conclusion, the use of a high-throughput screening, in silico data handling and zebrafish testing may constitute a paradigm for rapid and integrated ENM toxicological screening.

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Metadata

Authors
George, S., Xia, T., Rallo, R., Zhao, Y., Ji, Z., Lin, S., Wang, X., Zhang, H., France, B., Schoenfeld, D., Damoiseaux, R., Liu, R., Lin, S., Bradley, K. A., Cohen, Y., & Nel, A. E.
Venue
ACS Nano
Published
2011-02-16
Volume
5
Issue
3
Pages
1805-1817
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
OpenAlex
W2036661308
Cited by
326
References
45
FWCI
18.13
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Use of a High-Throughput Screening Approach Coupled with In Vivo Zebrafish Embryo Screening To Develop Hazard Ranking for Engineered Nanomaterials. https://app.cochat.ai/papers/10.1021/nn102734s
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George, S., Xia, T., Rallo, R., Zhao, Y., Ji, Z., Lin, S., Wang, X., Zhang, H., France, B., Schoenfeld, D., Damoiseaux, R., Liu, R., Lin, S., Bradley, K. A., Cohen, Y., & Nel, A. E. (2011). Use of a High-Throughput Screening Approach Coupled with In Vivo Zebrafish Embryo Screening To Develop Hazard Ranking for Engineered Nanomaterials. ACS Nano. https://doi.org/10.1021/nn102734s

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