title: Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow gold nanospheres.
abstract: OBJECTIVE
  Gold nanoparticles have attracted enormous interest as potential theranostic agents. However, little is known about the long-term elimination and systemic toxicity of gold nanoparticles in the literature. Hollow gold nanospheres (HAuNS) is a class of photothermal conducting agent that have shown promises in photoacoustic imaging, photothermal ablation therapy, and drug delivery. It's very necessary to make clear the biosafety of HAuNS for its further application.
  
  
  METHODS
  We investigated the cytotoxicity, complement activation, and platelet aggregation of polyethylene glycol (PEG)-coated HAuNS (PEG-HAuNS, average diameter of 63 nm) in vitro and their pharmacokinetics, biodistribution, organ elimination, hematology, clinical chemistry, acute toxicity, and chronic toxicity in mice.
  
  
  RESULTS
  PEG-HAuNS did not induce detectable activation of the complement system and did not induce detectable platelet aggregation. The blood half-life of PEG-HAuNS in mice was 8.19 ± 1.4 hr. The single effective dose of PEG-HAuNS in photothermal ablation therapy was determined to be 12.5 mg/kg. PEG-HAuNS caused no adverse effects after 10 daily intravenous injections over a 2-week period at a dose of 12.5 mg/kg per injection (accumulated dose: 125 mg/kg). Quantitative analysis of the muscle, liver, spleen, and kidney revealed that the levels of Au decreased 45.2%, 28.6%, 41.7%, and 40.8%, respectively, from day 14 to day 90 after the first intravenous injection, indicating that PEG-HAuNS was slowly cleared from these organs in mice.
  
  
  CONCLUSIONS
  Our data support the use of PEG-HAuNS as a promising photothermal conducting agent.
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.forename: Jialin
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Cancer Systems Imaging, Unit 59, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. cvpelt@comcast.net.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Van Pelt
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D001772:Blood Cell Count; D003167:Complement Activation / Q000187:drug effects; D003301:Copper Radioisotopes; D005260:Female; D006046:Gold / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D018374:LLC-PK1 Cells; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D054118:Nanospheres / Q000378:metabolism* / Q000633:toxicity*; D010051:Ovarian Neoplasms / Q000473:pathology; D010316:Particle Size; D010974:Platelet Aggregation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity*; D013154:Spleen / Q000473:pathology; D013552:Swine; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003301:Copper Radioisotopes; D011092:Polyethylene Glycols; D006046:Gold