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Cellular binding, uptake and biotransformation of silver nanoparticles in human T lymphocytes


Our knowledge of uptake, toxicity and detoxification mechanisms as related to nanoparticles’ (NPs’) characteristics remains incomplete. Here we combine the analytical power of three advanced techniques to study the cellular binding and uptake and the intracellular transformation of silver nanoparticles (AgNPs): single-particle inductively coupled mass spectrometry, mass cytometry and synchrotron X-ray absorption spectrometry. Our results show that although intracellular and extracellularly bound AgNPs undergo major transformation depending on their primary size and surface coating, intracellular Ag in 24 h AgNP-exposed human lymphocytes exists in nanoparticulate form. Biotransformation of AgNPs is dominated by sulfidation, which can be viewed as one of the cellular detoxification pathways for Ag. These results also show that the toxicity of AgNPs is primarily driven by internalized Ag. In fact, when toxicity thresholds are expressed as the intracellular mass of Ag per cell, differences in toxicity between NPs of different coatings and sizes are minimized. The analytical approach developed here has broad applicability in different systems where the aim is to understand and quantify cell–NP interactions and biotransformation.

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Fig. 1: Representative transmission electron microscopy (TEM) images and size measurements of AgNPs used in the study.
Fig. 2: Cellular binding and uptake of Ag in AgNP exposed cells at single cell and population level.
Fig. 3: Speciation of cell-surface-associated and intracellular Ag in AgNP-exposed human T lymphocytes according to synchrotron XAS analysis.
Fig. 4: The sp-ICP-MS results.

Data availability

The data that support the findings reported in this study are available from the corresponding author upon reasonable request.


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We thank A. Mitchell for his help with Cy-TOF and S. Ritch and G. Brunetti for their help with ICP-MS. A part of the work was undertaken on the XAS beamline at the Australian Synchrotron, part of the Australian Nuclear Science and Technology Organisation (ANSTO). We acknowledge support for N.H.V. from the Melbourne Centre for Nanofabrication, the Victorian Node of the Australian National Fabrication Facility.

Author information




N.H.V. and E.L. conceived the research. A.M. and A.I. designed and conducted the experiments and contributed equally to the experimental work. A.M., A.I. and C.L.D. analysed the experimental results. N.H.V. and E.L. supervised the project. A.M., A.I. and C.L.D. drafted the manuscript, and N.H.V. and E.L. provided input and revisions.

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Correspondence to Enzo Lombi.

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The authors declare no competing interests.

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Peer review information Nature Nanotechnology thanks Qiangbin Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Information

Supplementary Tables 1 and 2 and Figs. 1–7.

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Malysheva, A., Ivask, A., Doolette, C.L. et al. Cellular binding, uptake and biotransformation of silver nanoparticles in human T lymphocytes. Nat. Nanotechnol. (2021).

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