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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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.
The authors declare no competing interests.
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 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. 16, 926–932 (2021). https://doi.org/10.1038/s41565-021-00914-3
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