title: Storage of gold nanoclusters in muscle leads to their biphasic in vivo clearance.
abstract: Ultrasmall gold nanoclusters (Au NCs) show great potential in biomedical applications. Long-term biodistribution, retention, toxicity, and pharmacokinetics profiles are pre-requisites in their potential clinical applications. Here, the biodistribution, clearance, and toxicity of one widely used Au NC species-glutathione-protected Au NCs or GSH-Au NCs-are systematically investigated over a relatively long period of 90 days in mice. Most of the Au NCs are cleared at 30 days post injection (p.i.) with a major accumulation in liver and kidney. However, it is surprising that an abnormal increase of the Au amount in the heart, liver, spleen, lung, and testis is observed at 60 and 90 days p.i., indicating that the injected Au NCs form a V-shaped time-dependent distribution profile in various organs. Further investigations reveal that Au NCs are steadily accumulating in the muscle in the first 30 days p.i., and the as-stored Au NCs gradually release into the blood in 30-90 days p.i., which induces a re-distribution and re-accumulation of Au NCs in all blood-rich organs. Further hematology and biochemistry studies show that the re-accumulation of Au NCs still causes some liver toxicity at 30 days p.i. The muscle storage and subsequent release may give rise to the potential accumulation and toxicity risk of functional nanomaterials over long periods of time.
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Luo
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Song
authors.forename: Xiu
authors.initials: X
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Long
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Sun
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Zheng
authors.forename: David Tai
authors.initials: DT
authors.lastname: Leong
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D006046:Gold / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009132:Muscles / Q000737:chemistry*; D049329:Nanostructures; D014018:Tissue Distribution
chemical_list: D006046:Gold
keywords: biodistribution; cytotoxicity; gold nanoclusters; muscle storage; re-accumulation