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

Di Wei 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 Kilburn & 3 others Laurence Hurley, Nicole Smith, Killugudi Swaminatha Iyer

Research output: Contribution to journalArticle

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.
LanguageEnglish
JournalNature Nanotechnology
DOIs
StateE-pub ahead of print - 8 Oct 2018

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Nanorods
Gold
nanorods
DNA
deoxyribonucleic acid
gold
gene expression
Gene expression
Chemical speciation
Medical nanotechnology
inorganic materials
Poisons
conjugation
Sulfhydryl Compounds
thiols
Nanostructures
Visualization
actuators
Cells
nuclei

Cite this

@article{bf252096d2f647d18ce162c0ac60005c,
title = "Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA",
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.",
author = "Ho, {Di Wei} and Jessica Kretzmann and Marck Norret and Priyanka Toshniwal and Veder, {Jean Pierre} and Haibo Jiang and Paul Guagliardo and Munshi, {Alaa Mahdi A} and Reena Chawla and Cameron Evans and Tristan Clemons and Michelle Nguyen and Amy Kretzmann and Amanda Blythe and Martin Saunders and Michael Archer and Melinda Fitzgerald and Jeffrey Keelan and Charles Bond and Matthew Kilburn and Laurence Hurley and Nicole Smith and {Swaminatha Iyer}, Killugudi",
year = "2018",
month = "10",
day = "8",
doi = "10.1038/s41565-018-0272-2",
language = "English",
journal = "Nature Nanotechnology",
issn = "1748-3387",
publisher = "Nature Publishing Group - Macmillan Publishers",

}

Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA. / Ho, Di Wei; Kretzmann, Jessica; Norret, Marck; Toshniwal, Priyanka; Veder, Jean Pierre; Jiang, Haibo; Guagliardo, Paul; Munshi, Alaa Mahdi A; Chawla, Reena; Evans, Cameron; Clemons, Tristan; Nguyen, Michelle; Kretzmann, Amy; Blythe, Amanda; Saunders, Martin; Archer, Michael; Fitzgerald, Melinda; Keelan, Jeffrey; Bond, Charles; Kilburn, Matthew; Hurley, Laurence; Smith, Nicole; Swaminatha Iyer, Killugudi.

In: Nature Nanotechnology, 08.10.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intracellular speciation of gold nanorods alters the conformational dynamics of genomic DNA

AU - Ho,Di Wei

AU - Kretzmann,Jessica

AU - Norret,Marck

AU - Toshniwal,Priyanka

AU - Veder,Jean Pierre

AU - Jiang,Haibo

AU - Guagliardo,Paul

AU - Munshi,Alaa Mahdi A

AU - Chawla,Reena

AU - Evans,Cameron

AU - Clemons,Tristan

AU - Nguyen,Michelle

AU - Kretzmann,Amy

AU - Blythe,Amanda

AU - Saunders,Martin

AU - Archer,Michael

AU - Fitzgerald,Melinda

AU - Keelan,Jeffrey

AU - Bond,Charles

AU - Kilburn,Matthew

AU - Hurley,Laurence

AU - Smith,Nicole

AU - Swaminatha Iyer,Killugudi

PY - 2018/10/8

Y1 - 2018/10/8

N2 - 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.

AB - 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.

U2 - 10.1038/s41565-018-0272-2

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JO - Nature Nanotechnology

T2 - Nature Nanotechnology

JF - Nature Nanotechnology

SN - 1748-3387

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