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Toxic effects and biodistribution of ultrasmall gold nanoparticles

Abstract

Gold nanoparticles (AuNPs) have been extensively explored in biomedical applications, for example as drug carriers, contrast agents, or therapeutics. However, AuNP can exhibit cytotoxic profile, when the size is below 2 nm (ultrasmall AuNP; usAuNP) and when the stabilizing ligands allow for access to the gold surface either for the direct interaction with biomolecules or for catalytic activity of the unshielded gold surface. Furthermore, usAuNP exhibits significantly different biodistribution and enhanced circulation times compared to larger AuNP. This review gives an overview about the synthesis and the physico-chemical properties of usAuNP and, thereby, focusses on 1.4 nm sized AuNP, which are derived from the compound Au55(PPh3)12Cl6 and which are the most intensively studied usAuNP in the field. This part is followed by a summary of the toxic properties of usAuNP, which include in vitro cytotoxicity tests on different cell lines, electrophysiological tests following FDA guidelines as well as studies on antibacterial effects. Finally, the biodistribution and pharmacokinetics of ultrasmall AuNP are discussed and compared to the properties of more biocompatible, larger AuNP.

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Fig. 1

Reprinted from ref. Corain et al. (2008) with permission from Elsevier Science

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Reprinted from ref. Schmid (2008) with permission from the Royal Society of Chemistry

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Reprinted from ref. Corain et al. (2008) with permission from Elsevier

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Reprinted from ref. Schmid (2008) with permission from the Royal Society of Chemistry

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a Reprinted with permission from ref. Schmid (1992). Copyright (1992) American Chemical Society. b Reprinted with permission from ref. Schmid et al. (2000) from John Wiley and Sons

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Reprinted from ref. Boyen et al. (2002) with permission from The American Association for the Advancement of Science

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Reprinted from Bezryadin et al. (1997) with the permission of AIP Publishing

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With kind permission from Springer Science + Business Media: Chi et al. (1998)

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Adapted from ref. Schmid (2008) with permission from the Royal Society of Chemistry

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Reprinted from ref. Zhang et al. (2003) with permission from American Chemical Society

Fig. 12

a Reprinted from ref. Schmid (2008) with permission from the Royal Society of Chemistry. b Reprinted from ref. Zhang et al. (2003) with permission from American Chemical Society

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Reprinted from Smith et al. (1997) Copyright (1997), with permission from Elsevier

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b Figure reprinted from Liu et al. (2003) with kind permission from John Wiley and Sons. c Figure reprinted from Tsoli et al. (2005) with kind permission from John Wiley and Sons

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Figure reprinted from Pan et al. (2007) with kind permission from John Wiley and Sons

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Reprinted from Broda et al. (2016b) Copyright (2016), with permission from Elsevier

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Figure reprinted from Pan et al. (2009) with kind permission from John Wiley and Sons

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Figure reprinted from Pan et al. (2009) with kind permission from John Wiley and Sons

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Reprinted from Leifert et al. (2013a, b) with kind permission of PNAS

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Figure reprinted from Broda et al. (2016a) with kind permission from John Wiley and Sons

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Figure reprinted from Broda et al. (2016a) with kind permission from John Wiley and Sons

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Figure reprinted from Boda et al. (2015) with kind permission from John Wiley and Sons

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Reprinted by permission from Macmillan Publishers Ltd: Nature Nanotechnology Kreyling et al. (2015) copyright (2015)

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Figure reprinted from Semmler-Behnke et al. (2014)

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Correspondence to Günter Schmid.

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Schmid, G., Kreyling, W.G. & Simon, U. Toxic effects and biodistribution of ultrasmall gold nanoparticles. Arch Toxicol 91, 3011–3037 (2017). https://doi.org/10.1007/s00204-017-2016-8

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Keywords

  • Gold nanoparticle
  • Cytotoxicity
  • Biodistribution
  • Pharamcokinetics