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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.

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Localisation of AuNPs within specific mouse tissues following IP injection.Scanning electron microscopy (SEM) images of AuNPs in adipose tissue (A, B, C) and liver sections (D, E, F) at 1 h (A, D), 24 h (B, E), and 72 h (C, F) post AuNP injection (Mag 2.01K x).
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pone-0058208-g002: Localisation of AuNPs within specific mouse tissues following IP injection.Scanning electron microscopy (SEM) images of AuNPs in adipose tissue (A, B, C) and liver sections (D, E, F) at 1 h (A, D), 24 h (B, E), and 72 h (C, F) post AuNP injection (Mag 2.01K x).

Mentions: A time-dependent pattern of AuNP distribution was noted within the abdominal fat and liver. AuNPs were located predominantly at the edge of the fat tissue (Figure 1B), with few clusters seen deep into the tissue between the adipocytes, at 1 h and 24 h (Figure 2A, B). At 72 h, AuNPs were seen to migrate further into the adipose tissue. They tended to accumulate within the connective tissue between adipocytes (Figure 2C). AuNPs on the outside edges of the tissue was visibly reduced. Although the location of the AuNPs within the adipose tissue appeared to change with time, there was however, no noticeable decrease in number of AuNP over the 72 h period.


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)

Localisation of AuNPs within specific mouse tissues following IP injection.Scanning electron microscopy (SEM) images of AuNPs in adipose tissue (A, B, C) and liver sections (D, E, F) at 1 h (A, D), 24 h (B, E), and 72 h (C, F) post AuNP injection (Mag 2.01K x).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0058208-g002: Localisation of AuNPs within specific mouse tissues following IP injection.Scanning electron microscopy (SEM) images of AuNPs in adipose tissue (A, B, C) and liver sections (D, E, F) at 1 h (A, D), 24 h (B, E), and 72 h (C, F) post AuNP injection (Mag 2.01K x).
Mentions: A time-dependent pattern of AuNP distribution was noted within the abdominal fat and liver. AuNPs were located predominantly at the edge of the fat tissue (Figure 1B), with few clusters seen deep into the tissue between the adipocytes, at 1 h and 24 h (Figure 2A, B). At 72 h, AuNPs were seen to migrate further into the adipose tissue. They tended to accumulate within the connective tissue between adipocytes (Figure 2C). AuNPs on the outside edges of the tissue was visibly reduced. Although the location of the AuNPs within the adipose tissue appeared to change with time, there was however, no noticeable decrease in number of AuNP over the 72 h period.

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