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

    273281.pdf (4.926Mb)
    Access Status
    Open access
    Authors
    Ho, D.
    Kretzmann, J.
    Norret, M.
    Toshniwal, P.
    Veder, Jean-Pierre
    Jiang, H.
    Guagliardo, P.
    Munshi, A.
    Chawla, R.
    Evans, C.
    Clemons, T.
    Nguyen, M.
    Kretzmann, A.
    Blythe, A.
    Saunders, M.
    Archer, M.
    Fitzgerald, Melinda
    Keelan, J.
    Bond, C.
    Kilburn, M.
    Hurley, L.
    Smith, N.
    Iyer, K.
    Date
    2018
    Type
    Journal Article
    
    Metadata
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    Citation
    Ho, D. and Kretzmann, J. and Norret, M. and Toshniwal, P. and Veder, J. and Jiang, H. and Guagliardo, P. et al. 2018. Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA. Nature Nanotechnology. 13: pp. 1148-1153.
    Source Title
    Nature Nanotechnology
    DOI
    10.1038/s41565-018-0272-2
    ISSN
    1748-3387
    School
    John de Laeter Centre
    Curtin Health Innovation Research Institute
    URI
    http://hdl.handle.net/20.500.11937/71376
    Collection
    • Curtin Research Publications
    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.

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