Gold nanorods (GNRs) are one of the most widely explored and well documented inorganic materials in nanomedicine, with applications in diagnostics, therapeutics and sensing. One of the reasons for such wide-spread use of GNRs is that they have repeatedly been reported as inert and non-cytotoxic. However, it has also been documented that exposure to GNRs can result in alterations in gene regulation, although the mechanisms remain unknown. Gene expression profiles are highly dependent on complex interactions between DNA-binding proteins and genomic sequences. In addition to sequence-specific interactions, sequence dependent structural dynamics of DNA also play a significant role in DNA-protein interactions. The stability of sequence-dependent dynamic secondary structures of DNA, such as G-quadruplex DNA, is highly influenced by the immediate microenvironment of surrounding regions.<br/>With a focus on conformational dynamics of secondary structures in genomic DNA we evaluate the potential of popular gold-thiol chemistry, used to engineer gold nanomaterials for intracellular applications, to alter the microenvironment within the nucleus. Our results confirm that GNR exposure is associated with an overall alteration in the conformational dynamics of genomic DNA, which can potentially play an important role in dictating changes in gene expression. We conclude that in order to develop translatable technologies using gold nanomaterials, it is essential to go beyond coarse cytotoxicity evaluations and conduct detailed <i>in situ</i> analysis of changes within the genomic environment.

Interaction of gold nanorods with genomic DNA

254th National Meeting (2017)

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