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

Diwei Ho, Jessica Kretzmann, Marck Norret, Priyanka Toshniwal, Jean Pierre Veder, Haibo Jiang, Paul Guagliardo, Alaa Mahdi A Munshi, Reena Chawla, Cameron Evans, Tristan Clemons, Michelle Nguyen, Amy Kretzmann, Amanda Blythe, Martin Saunders, Michael Archer, Melinda Fitzgerald, Jeffrey Keelan, Charles Bond, Matthew KilburnLaurence Hurley, Nicole Smith, Killugudi Swaminatha Iyer

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 cyto- toxic and localize within cytoplasmic vesicles following endo- cytosis, with no nuclear localization2,3, but other studies have reported alterations in gene expression profiles in cells fol- lowing 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 specia- tion process of gold nanorods, we show that the commonly used Au–thiol conjugation, which is important for maintain- ing 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 trig- gers alteration of gene expression in human cells. We demon- strate this using quantitative visualization of ubiquitous DNA G-quadruplex structures, which are sensitive to ionic imbal- ances, as an indicator of the formation of structural altera- tions in genomic DNA.
Original languageEnglish
JournalNature Nanotechnology
Volume13
Issue number2
Early online date8 Oct 2018
DOIs
Publication statusPublished - Dec 2018

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