Meta-analysis of cellular toxicity for cadmium-containing quantum dots

Abstract

Understanding the relationships between the physicochemical properties of engineered nanomaterials and their toxicity is critical for environmental and health risk analysis. However, this task is confounded by material diversity, heterogeneity of published data and limited sampling within individual studies. Here, we present an approach for analysing and extracting pertinent knowledge from published studies focusing on the cellular toxicity of cadmium-containing semiconductor quantum dots. From 307 publications, we obtain 1,741 cell viability-related data samples, each with 24 qualitative and quantitative attributes describing the material properties and experimental conditions. Using random forest regression models to analyse the data, we show that toxicity is closely correlated with quantum dot surface properties (including shell, ligand and surface modifications), diameter, assay type and exposure time. Our approach of integrating quantitative and categorical data provides a roadmap for interrogating the wide-ranging toxicity data in the literature and suggests that meta-analysis can help develop methods for predicting the toxicity of engineered nanomaterials.

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Figure 1: QD structure, meta-analysis workflow and compiled QD data.
Figure 2: IC50 values (red) and dosage range used (blue) for major QD core/shell structures.
Figure 3: RF analysis and models.
Figure 4: QD similarity network based on the RF model for cell viability using the six most significant attributes.
Figure 5: Conditional dependence of QD IC50 on surface ligand and/or QD diameter.

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Acknowledgements

I.L.M. acknowledges the Naval Research Laboratory Nanosciences Institute and the Defense Threat Reduction Agency Joint Science and Technology Office Military Interdepartmental Purchase Request no. B112582M. This study is also based on work supported by the National Science Foundation and the Environmental Protection Agency under Cooperative Agreement no. DBI-0830117. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation or the Environmental Protection Agency. This work has not been subjected to EPA review and no official endorsement should be inferred. Computational cluster support by the UCLA WaTeR center is also acknowledged.

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I.L.M., Y.C., R.L., E.O. and A.N. conceived the study. E.O., K.B.G. and I.L.M. searched the literature, extracted data, identified attributes and prepared data for analysis. E.O. developed the methodology for converting QD concentrations. R.L., M.B. and Y.C. analysed the data and developed the reported models and attribute significance. I.L.M., E.O., Y.C. and R.L. co-wrote the paper with input from all authors.

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Correspondence to Rong Liu or Yoram Cohen or Igor L. Medintz.

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The authors declare no competing financial interests.

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Oh, E., Liu, R., Nel, A. et al. Meta-analysis of cellular toxicity for cadmium-containing quantum dots. Nature Nanotech 11, 479–486 (2016). https://doi.org/10.1038/nnano.2015.338

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