Abstract
ObjectivesGold 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.MethodsMale 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.ResultsAt 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).ConclusionOur 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.
Highlights
Biomedical applications of gold nanoparticles (AuNPs) are rapidly increasing due to their attractive properties of relatively low cytotoxicity, a high capacity to target cells, readily functionalized surfaces and a tunable optical absorption peak
AuNP-based delivery systems are being widely explored for use in cancer chemotherapy treatment as they offer increased drug efficacy with low toxicity to healthy tissue, high biocompatibility, along with versatile production methods, which enable custom design [1]
Endotoxin screening of the AuNPs The endotoxin screening revealed that there was no detectable level of endotoxin contamination present within the AuNP solutions, with absorbance readings falling below detectable levels (,0.005 EU/mL)
Summary
Biomedical applications of gold nanoparticles (AuNPs) are rapidly increasing due to their attractive properties of relatively low cytotoxicity, a high capacity to target cells, readily functionalized surfaces and a tunable optical absorption peak. Gold compounds such as gold sodium thiomalate have long been used to treat some forms of arthritis [1,2] but the gold in these substances is in the more active oxidized form whereas in nanoparticles it is present as the comparatively inert metallic form. AuNPs can be synthesized in a range of morphologies, most current activity is focused on exploiting either nanospheres and nanorods
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