Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles

Qiyue Xia,1,2,* Jinxing Huang,1,* Qiyi Feng,1 Xuanming Chen,1 Xinyi Liu,1 Xiaojie Li,1 Ting Zhang,3 Shuwen Xiao,1 Hongxia Li,1 Zhihui Zhong,3,4 Kai Xiao1,41National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan Univ...

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Autores principales:	Xia Q, Huang J, Feng Q, Chen X, Liu X, Li X, Zhang T, Xiao S, Li H, Zhong Z, Xiao K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Gold nanoparticles particle size uptake toxicity biodistribution Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8ee272d0bd724eaa9eb4be08ef964a7f
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spelling	oai:doaj.org-article:8ee272d0bd724eaa9eb4be08ef964a7f2021-12-02T08:18:07ZSize- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles1178-2013https://doaj.org/article/8ee272d0bd724eaa9eb4be08ef964a7f2019-08-01T00:00:00Zhttps://www.dovepress.com/size--and-cell-type-dependent-cellular-uptake-cytotoxicity-and-in-vivo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Qiyue Xia,1,2,* Jinxing Huang,1,* Qiyi Feng,1 Xuanming Chen,1 Xinyi Liu,1 Xiaojie Li,1 Ting Zhang,3 Shuwen Xiao,1 Hongxia Li,1 Zhihui Zhong,3,4 Kai Xiao1,41National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China; 2Toxicology Department, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan Province, China; 3Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; 4Sichuan Kangcheng Biotech Co., Ltd, Chengdu, Sichuan Province, ChinaCorrespondence: Kai XiaoNational Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 28 Gaopeng Ave, High-Tech Development Zone, Chengdu 610041, Sichuan Province, People’s Republic of ChinaTel +86 288 332 6313Fax +86 288 517 3043Email xiaokaikaixiao@scu.edu.cn*These authors contributed equally to this workBackground: Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated.Purpose: The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo.Results: Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs  but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice.Conclusion: Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.Keywords: gold nanoparticles, particle size, uptake, toxicity, biodistributionXia QHuang JFeng QChen XLiu XLi XZhang TXiao SLi HZhong ZXiao KDove Medical PressarticleGold nanoparticlesparticle sizeuptaketoxicitybiodistributionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6957-6970 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gold nanoparticles particle size uptake toxicity biodistribution Medicine (General) R5-920
spellingShingle	Gold nanoparticles particle size uptake toxicity biodistribution Medicine (General) R5-920 Xia Q Huang J Feng Q Chen X Liu X Li X Zhang T Xiao S Li H Zhong Z Xiao K Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
description	Qiyue Xia,1,2,* Jinxing Huang,1,* Qiyi Feng,1 Xuanming Chen,1 Xinyi Liu,1 Xiaojie Li,1 Ting Zhang,3 Shuwen Xiao,1 Hongxia Li,1 Zhihui Zhong,3,4 Kai Xiao1,41National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China; 2Toxicology Department, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan Province, China; 3Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; 4Sichuan Kangcheng Biotech Co., Ltd, Chengdu, Sichuan Province, ChinaCorrespondence: Kai XiaoNational Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 28 Gaopeng Ave, High-Tech Development Zone, Chengdu 610041, Sichuan Province, People’s Republic of ChinaTel +86 288 332 6313Fax +86 288 517 3043Email xiaokaikaixiao@scu.edu.cn*These authors contributed equally to this workBackground: Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated.Purpose: The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo.Results: Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs  but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice.Conclusion: Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.Keywords: gold nanoparticles, particle size, uptake, toxicity, biodistribution
format	article
author	Xia Q Huang J Feng Q Chen X Liu X Li X Zhang T Xiao S Li H Zhong Z Xiao K
author_facet	Xia Q Huang J Feng Q Chen X Liu X Li X Zhang T Xiao S Li H Zhong Z Xiao K
author_sort	Xia Q
title	Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
title_short	Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
title_full	Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
title_fullStr	Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
title_full_unstemmed	Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
title_sort	size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8ee272d0bd724eaa9eb4be08ef964a7f
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Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles

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