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 cytotoxic and localize within cytoplasmic vesicles following endocytosis, with no nuclear localization2,3, but other studies...

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Main 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.
Format: Journal Article
Published: Macmillan Publishers Limited 2018
Online Access:http://hdl.handle.net/20.500.11937/71376
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author 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.
author_facet 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.
author_sort Ho, D.
building Curtin Institutional Repository
collection Online Access
description 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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format Journal Article
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institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T10:47:58Z
publishDate 2018
publisher Macmillan Publishers Limited
recordtype eprints
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spelling curtin-20.500.11937-713762019-04-10T05:21:13Z Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA 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. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/71376 10.1038/s41565-018-0272-2 Macmillan Publishers Limited fulltext
spellingShingle 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.
Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA
title Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA
title_full Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA
title_fullStr Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA
title_full_unstemmed Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA
title_short Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA
title_sort intracellular speciation of gold nanorods alters the conformational dynamics of genomic dna
url http://hdl.handle.net/20.500.11937/71376