In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice

• Published in: PloS one 2013-02, Vol.8 (2), p.e58208
• Main Authors: Chen, Hui, Dorrigan, Alisha, Saad, Sonia, Hare, Dominic J, Cortie, Michael B, Valenzuela, Stella M
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animal tissues; Animals; Biocompatibility; Biology; Body fat; Body weight; Chemical compounds; Custom design; Cytokines; Cytokines - genetics; Eating - drug effects; Electron microscopy; Energy intake; Gene Expression Regulation - drug effects; Gold; Gold - administration & dosage; Gold - chemistry; Gold - pharmacokinetics; Gold - toxicity; In vivo methods and tests; Inflammation; Inflammation - metabolism; Injection; Injections, Intraperitoneal; Insulin resistance; Interleukin 6; Kidneys; Liver; Macrophages; Male; Materials Science; Metal Nanoparticles - toxicity; Mice; Mice, Inbred C57BL; mRNA; Nanoparticles; Obesity; Organ Size - drug effects; Organs; Pharmacology; Polyethylene glycol; Proteins; Rheumatoid arthritis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Studies; Tissue Distribution; Toxicity; Toxicity testing; Toxicity Tests, Acute; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0058208

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. 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. 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). 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.