title: In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice.
abstract: OBJECTIVE
  Gold nanoparticles (AuNPs) of 21 nm have been previously well characterized in vitro for their capacity to target macrophages via active uptake. However, the short-term impact of such AuNPs on physiological systems, in particular resident macrophages located in fat tissue in vivo, is largely unknown. This project investigated the distribution, organ toxicity and changes in inflammatory cytokines within the adipose tissue after mice were exposed to AuNPs.
  
  
  METHODS
  Male C57BL/6 mice were injected intraperitoneally (IP) with a single dose of AuNPs (7.85 μg AuNPs/g). Body weight and energy intake were recorded daily. Tissues were collected at 1 h, 24 h and 72 h post-injection to test for organ toxicity. AuNP distribution was examined using electron microscopy. Proinflammatory cytokine expression and macrophage number within the abdominal fat pad were determined using real-time PCR.
  
  
  RESULTS
  At 72 hours post AuNP injection, daily energy intake and body weight were found to be similar between Control and AuNP treated mice. However, fat mass was significantly smaller in AuNP-treated mice. Following IP injection, AuNPs rapidly accumulated within the abdominal fat tissue and some were seen in the liver. A reduction in TNFα and IL-6 mRNA levels in the fat were observed from 1 h to 72 h post AuNP injection, with no observable changes in macrophage number. There was no detectable toxicity to vital organs (liver and kidney).
  
  
  CONCLUSIONS
  Our 21 nm spherical AuNPs caused no measurable organ or cell toxicity in mice, but were correlated with significant fat loss and inhibition of inflammatory effects. With the growing incidence of obesity and obesity-related diseases, our findings offer a new avenue for the potential development of gold nanoparticles as a therapeutic agent in the treatment of such disorders.
authors.affiliation: School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Alisha
authors.initials: A
authors.lastname: Dorrigan
authors.forename: Sonia
authors.initials: S
authors.lastname: Saad
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cortie
authors.forename: Stella M
authors.initials: SM
authors.lastname: Valenzuela
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000235:genetics; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D007249:Inflammation / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D006046:Gold