title: Cytotoxicity of nucleus-targeting fluorescent gold nanoclusters.
abstract: Gold nanoclusters (AuNCs) with ultra small sizes and unique fluorescence properties have shown promising potential for imaging the nuclei of living cells. However, little is known regarding the potential cytotoxicity of AuNCs after they enter the cell nucleus. The aim of this study is to investigate whether and how nucleus-targeting AuNCs affect the normal functioning of cells. Highly stable, water-soluble and bright fluorescent Au25NCs (the core of each nanocluster is composed of 25 gold atoms) were synthesized. Specific targeting of Au25NCs to the cell nucleus was achieved by conjugating the TAT peptide to the Au25NCs. Cell viability, cell morphology, cell apoptosis/necrosis, reactive oxygen species (ROS) level and mitochondrial membrane potential examinations were performed on different cell lines exposed to the nucleus-targeting Au25NCs. We found that the nucleus-targeting Au25NCs caused cell apoptosis in a dose-dependent manner. A possible mechanism for the cytotoxicity of the nucleus-targeting Au25NCs was proposed as follows: the nucleus-targeting Au25NCs induce the production of ROS, resulting in the oxidative degradation of mitochondrial components, in turn leading to apoptosis via a mitochondrial damage pathway. This work facilitates a better understanding of the toxicity of AuNCs, especially nucleus-targeting AuNCs.
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, State Key Laboratory of Virology, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan, 430072, P. R. China. dwpang@whu.edu.cn.
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Zhao
authors.forename: Ran
authors.initials: R
authors.lastname: Cui
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhang
authors.forename: Mingxi
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Xie
authors.forename: Dai-Wen
authors.initials: DW
authors.lastname: Pang
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004285:Dogs; D005456:Fluorescent Dyes / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D053078:Membrane Potential, Mitochondrial; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D008970:Molecular Weight; D009336:Necrosis; D010100:Oxygen / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D012995:Solubility; D014709:Vero Cells; D014867:Water / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides; D017382:Reactive Oxygen Species; D014867:Water; D006046:Gold; D010100:Oxygen