title: Mitochondrial dysfunction induced by ultra-small silver nanoclusters with a distinct toxic mechanism.
abstract: As noble metal nanoclusters (NCs) are widely employed in nanotechnology, their potential threats to human and environment are relatively less understood. Herein, the biological effects of ultra-small silver NCs coated by bovine serum albumin (BSA) (Ag-BSA NCs) on isolated rat liver mitochondria were investigated by testing mitochondrial swelling, membrane permeability, ROS generation, lipid peroxidation and respiration. It was found that Ag-BSA NCs induced mitochondrial dysfunction via synergistic effects of two different ways: (1) inducing mitochondrial membrane permeability transition (MPT) by interacting with the phospholipid bilayer of the mitochondrial membrane (not with specific MPT pore proteins); (2) damaging mitochondrial respiration by the generation of reactive oxygen species (ROS). As far as we know, this is the first report on the biological effects of ultra-small size nanoparticles (∼2 nm) at the sub-cellular level, which provides significant insights into the potential risks brought by the applications of NCs. It would inspire us to evaluate the potential threats of nanomaterials more comprehensively, even though they showed no obvious toxicity to cells or in vivo animal models. Noteworthy, a distinct toxic mechanism to mitochondria caused by Ag-BSA NCs was proposed and elucidated.
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Jia-Han
authors.initials: JH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Qi-Qi
authors.initials: QQ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China; Hubei Key Laboratory for Processing and Application of Catalytic Materials, Huanggang Normal University, Huanggang 438000, PR China. Electronic address: fljiang@whu.edu.cn.
authors.forename: Feng-Lei
authors.initials: FL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects; D008933:Mitochondrial Swelling / Q000187:drug effects; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000633:toxicity*; D012834:Silver / Q000737:chemistry / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D012710:Serum Albumin, Bovine; D012834:Silver
keywords: Biological effect; Mitochondria; Mitochondrial permeability transition; Noble metal nanoclusters; Ultra-small nanoparticles