Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA

Diwei Ho, Jessica A. Kretzmann, Marck Norret, Priyanka Toshniwal, Jean Pierre Veder, Haibo Jiang, Paul Guagliardo, Alaa M. Munshi, Reena Chawla, Cameron W. Evans, Tristan D. Clemons, Michelle Nguyen, Amy L. Kretzmann, Amanda J. Blythe, Martin Saunders, Michael Archer, Melinda Fitzgerald, Jeffrey A. Keelan, Charles S. Bond, Matt R. KilburnLaurence Hurley, Nicole M. Smith, K. Swaminathan Iyer

Research output: Contribution to journalLetter

6 Scopus citations

Abstract

Gold nanorods are one of the most widely explored inorganic materials in nanomedicine for diagnostics, therapeutics and sensing1. It has been shown that gold nanorods are not cytotoxic and localize within cytoplasmic vesicles following endocytosis, with no nuclear localization2,3, but other studies have reported alterations in gene expression profiles in cells following exposure to gold nanorods, via unknown mechanisms4. In this work we describe a pathway that can contribute to this phenomenon. By mapping the intracellular chemical speciation process of gold nanorods, we show that the commonly used Au–thiol conjugation, which is important for maintaining the noble (inert) properties of gold nanostructures, is altered following endocytosis, resulting in the formation of Au(i)–thiolates that localize in the nucleus5. Furthermore, we show that nuclear localization of the gold species perturbs the dynamic microenvironment within the nucleus and triggers alteration of gene expression in human cells. We demonstrate this using quantitative visualization of ubiquitous DNA G-quadruplex structures, which are sensitive to ionic imbalances, as an indicator of the formation of structural alterations in genomic DNA.

Original languageEnglish (US)
Pages (from-to)1148-1153
Number of pages6
JournalNature Nanotechnology
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

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  • Cite this

    Ho, D., Kretzmann, J. A., Norret, M., Toshniwal, P., Veder, J. P., Jiang, H., Guagliardo, P., Munshi, A. M., Chawla, R., Evans, C. W., Clemons, T. D., Nguyen, M., Kretzmann, A. L., Blythe, A. J., Saunders, M., Archer, M., Fitzgerald, M., Keelan, J. A., Bond, C. S., ... Iyer, K. S. (2018). Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA. Nature Nanotechnology, 13(12), 1148-1153. https://doi.org/10.1038/s41565-018-0272-2