title: Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy.
abstract: Gold nanoclusters (Au NCs) have exhibited great advantages in medical diagnostics and therapies due to their efficient renal clearance and high tumor uptake. The in vivo effects of the surface chemistry of Au NCs are important for the development of both nanobiological interfaces and potential clinical contrast reagents, but these properties are yet to be fully investigated. In this study, we prepared glutathione-protected Au NCs of a similar hydrodynamic size but with three different surface charges: positive, negative, and neutral. Their in vivo biodistribution, excretion, and toxicity were investigated over a 90-day period, and tumor uptake and potential application to radiation therapy were also evaluated. The results showed that the surface charge greatly influenced pharmacokinetics, particularly renal excretion and accumulation in kidney, liver, spleen, and testis. Negatively charged Au NCs displayed lower excretion and increased tumor uptake, indicating a potential for NC-based therapeutics, whereas positively charged clusters caused transient side effects on the peripheral blood system.
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin.
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Environment, Energy and Natural Resources Center, Department of Environmental Science and Engineering, Fudan University, Shanghai.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin.
authors.forename: Xiu
authors.initials: X
authors.lastname: Shen
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin.
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Sun
authors.affiliation: Department of Physics, School of Science, Tianjin Chengjian University.
authors.forename: Meili
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Physics, School of Science, Tianjin University, Tianjin, People's Republic of China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006046:Gold / Q000633:toxicity*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D006046:Gold; D005978:Glutathione
keywords: cancer therapy; gold clusters; in vivo toxicity; long-term