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

Chen H, Dorrigan A, Saad S, Hare DJ, Cortie MB, Valenzuela SM - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia.

ABSTRACT

Objectives: 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).

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Changes in mRNA cytokine expression levels in mouse abdominal fat tissue at different time points post IP injection of AuNPs.mRNA levels of (A) CD68, (B) TNFα and (C) IL-6 in abdominal fat at different time points post AuNPs injection. Results are expressed as mean ± SE, n = 4–8 in each group. *P<0.05, compared with Control group. CON, control; Au, AuNPs. The differences among groups were analysed using one-way ANOVA, followed by post hoc Fisher's Least Significance Difference tests.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585265&req=5

pone-0058208-g004: Changes in mRNA cytokine expression levels in mouse abdominal fat tissue at different time points post IP injection of AuNPs.mRNA levels of (A) CD68, (B) TNFα and (C) IL-6 in abdominal fat at different time points post AuNPs injection. Results are expressed as mean ± SE, n = 4–8 in each group. *P<0.05, compared with Control group. CON, control; Au, AuNPs. The differences among groups were analysed using one-way ANOVA, followed by post hoc Fisher's Least Significance Difference tests.

Mentions: The mRNA expression of the marker for macrophage cells, CD68, was not significantly changed over the 3 day period post-AuNP injection compared with the Control group (Figure 4A). However, TNFα mRNA expression was significantly reduced at the 1 h time point, which persisted until 3 days post AuNP injection (Figure 4B). Although IL-6 mRNA expression was also markedly down-regulated over the course of the experiment, it did not reach statistical significance (Figure 4C).


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

Chen H, Dorrigan A, Saad S, Hare DJ, Cortie MB, Valenzuela SM - PLoS ONE (2013)

Changes in mRNA cytokine expression levels in mouse abdominal fat tissue at different time points post IP injection of AuNPs.mRNA levels of (A) CD68, (B) TNFα and (C) IL-6 in abdominal fat at different time points post AuNPs injection. Results are expressed as mean ± SE, n = 4–8 in each group. *P<0.05, compared with Control group. CON, control; Au, AuNPs. The differences among groups were analysed using one-way ANOVA, followed by post hoc Fisher's Least Significance Difference tests.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585265&req=5

pone-0058208-g004: Changes in mRNA cytokine expression levels in mouse abdominal fat tissue at different time points post IP injection of AuNPs.mRNA levels of (A) CD68, (B) TNFα and (C) IL-6 in abdominal fat at different time points post AuNPs injection. Results are expressed as mean ± SE, n = 4–8 in each group. *P<0.05, compared with Control group. CON, control; Au, AuNPs. The differences among groups were analysed using one-way ANOVA, followed by post hoc Fisher's Least Significance Difference tests.
Mentions: The mRNA expression of the marker for macrophage cells, CD68, was not significantly changed over the 3 day period post-AuNP injection compared with the Control group (Figure 4A). However, TNFα mRNA expression was significantly reduced at the 1 h time point, which persisted until 3 days post AuNP injection (Figure 4B). Although IL-6 mRNA expression was also markedly down-regulated over the course of the experiment, it did not reach statistical significance (Figure 4C).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia.

ABSTRACT

Objectives: 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).

Conclusion: 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.

Show MeSH
Related in: MedlinePlus