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

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.