Molecular origin of AuNPs-induced cytotoxicity and mechanistic study

Abstract Gold nanoparticles (AuNPs) with diverse physicochemical properties are reported to affect biological systems differently, but the relationship between the physicochemical properties of AuNPs and their biological effects is not clearly understood. Here, we aimed to elucidate the molecular or...

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Autores principales:	Euiyeon Lee, Hyunjin Jeon, Minhyeong Lee, Jeahee Ryu, Chungwon Kang, Soyoun Kim, Junghyun Jung, Youngeun Kwon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d9678b87677403d97b1408957bf10d8
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spelling	oai:doaj.org-article:7d9678b87677403d97b1408957bf10d82021-12-02T16:08:04ZMolecular origin of AuNPs-induced cytotoxicity and mechanistic study10.1038/s41598-019-39579-32045-2322https://doaj.org/article/7d9678b87677403d97b1408957bf10d82019-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-39579-3https://doaj.org/toc/2045-2322Abstract Gold nanoparticles (AuNPs) with diverse physicochemical properties are reported to affect biological systems differently, but the relationship between the physicochemical properties of AuNPs and their biological effects is not clearly understood. Here, we aimed to elucidate the molecular origins of AuNP-induced cytotoxicity and their mechanisms, focusing on the surface charge and structural properties of modified AuNPs. We prepared a library of well-tailored AuNPs exhibiting various functional groups and surface charges. Through this work, we revealed that the direction or the magnitude of surface charge is not an exclusive factor that determines the cytotoxicity of AuNPs. We, instead, suggested that toxic AuNPs share a common structural characteristics of a hydrophobic moiety neighbouring the positive charge, which can induce lytic interaction with plasma membrane. Mechanistic study showed that the toxic AuNPs interfered with the formation of cytoskeletal structure to slow cell migration, inhibited DNA replication and caused DNA damage via oxidative stress to hinder cell proliferation. Gene expression analysis showed that the toxic AuNPs down-regulated genes associated with cell cycle processes. We discovered structural characteristics that define the cytotoxic AuNPs and suggested the mechanisms of their cytotoxicity. These findings will help us to understand and to predict the biological effects of modified AuNPs based on their physicochemical properties.Euiyeon LeeHyunjin JeonMinhyeong LeeJeahee RyuChungwon KangSoyoun KimJunghyun JungYoungeun KwonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Euiyeon Lee Hyunjin Jeon Minhyeong Lee Jeahee Ryu Chungwon Kang Soyoun Kim Junghyun Jung Youngeun Kwon Molecular origin of AuNPs-induced cytotoxicity and mechanistic study
description	Abstract Gold nanoparticles (AuNPs) with diverse physicochemical properties are reported to affect biological systems differently, but the relationship between the physicochemical properties of AuNPs and their biological effects is not clearly understood. Here, we aimed to elucidate the molecular origins of AuNP-induced cytotoxicity and their mechanisms, focusing on the surface charge and structural properties of modified AuNPs. We prepared a library of well-tailored AuNPs exhibiting various functional groups and surface charges. Through this work, we revealed that the direction or the magnitude of surface charge is not an exclusive factor that determines the cytotoxicity of AuNPs. We, instead, suggested that toxic AuNPs share a common structural characteristics of a hydrophobic moiety neighbouring the positive charge, which can induce lytic interaction with plasma membrane. Mechanistic study showed that the toxic AuNPs interfered with the formation of cytoskeletal structure to slow cell migration, inhibited DNA replication and caused DNA damage via oxidative stress to hinder cell proliferation. Gene expression analysis showed that the toxic AuNPs down-regulated genes associated with cell cycle processes. We discovered structural characteristics that define the cytotoxic AuNPs and suggested the mechanisms of their cytotoxicity. These findings will help us to understand and to predict the biological effects of modified AuNPs based on their physicochemical properties.
format	article
author	Euiyeon Lee Hyunjin Jeon Minhyeong Lee Jeahee Ryu Chungwon Kang Soyoun Kim Junghyun Jung Youngeun Kwon
author_facet	Euiyeon Lee Hyunjin Jeon Minhyeong Lee Jeahee Ryu Chungwon Kang Soyoun Kim Junghyun Jung Youngeun Kwon
author_sort	Euiyeon Lee
title	Molecular origin of AuNPs-induced cytotoxicity and mechanistic study
title_short	Molecular origin of AuNPs-induced cytotoxicity and mechanistic study
title_full	Molecular origin of AuNPs-induced cytotoxicity and mechanistic study
title_fullStr	Molecular origin of AuNPs-induced cytotoxicity and mechanistic study
title_full_unstemmed	Molecular origin of AuNPs-induced cytotoxicity and mechanistic study
title_sort	molecular origin of aunps-induced cytotoxicity and mechanistic study
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/7d9678b87677403d97b1408957bf10d8
work_keys_str_mv	AT euiyeonlee molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT hyunjinjeon molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT minhyeonglee molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT jeaheeryu molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT chungwonkang molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT soyounkim molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT junghyunjung molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy AT youngeunkwon molecularoriginofaunpsinducedcytotoxicityandmechanisticstudy
_version_	1718384665564282880

Molecular origin of AuNPs-induced cytotoxicity and mechanistic study

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