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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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Related in: MedlinePlus

AuNP distribution within mouse liver following IP injection.AuNPs in (A) the liver connective tissue and (B) a 5 µm capillary within the liver adipose tissue (Mag 5.00K x), and in (C) a Kupffer cell within the sinusoid of the liver (Mag 4.19K x).
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pone-0058208-g003: AuNP distribution within mouse liver following IP injection.AuNPs in (A) the liver connective tissue and (B) a 5 µm capillary within the liver adipose tissue (Mag 5.00K x), and in (C) a Kupffer cell within the sinusoid of the liver (Mag 4.19K x).

Mentions: In the liver, AuNPs were seen to be situated in and around the blood vessels (Figure 2D, E, F), suggesting that they had entered the vascular system and been transported to the liver via the blood circulation. At 72h, AuNPs were seen further away from sinusoids, being identified in and around hepatocytes. The AuNPs also appear to have been phagocytosed by Kupffer cells within the sinusoid as seen in Figure 3D, where a discrete cell body was visualised containing copious numbers of AuNP clusters.


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)

AuNP distribution within mouse liver following IP injection.AuNPs in (A) the liver connective tissue and (B) a 5 µm capillary within the liver adipose tissue (Mag 5.00K x), and in (C) a Kupffer cell within the sinusoid of the liver (Mag 4.19K x).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0058208-g003: AuNP distribution within mouse liver following IP injection.AuNPs in (A) the liver connective tissue and (B) a 5 µm capillary within the liver adipose tissue (Mag 5.00K x), and in (C) a Kupffer cell within the sinusoid of the liver (Mag 4.19K x).
Mentions: In the liver, AuNPs were seen to be situated in and around the blood vessels (Figure 2D, E, F), suggesting that they had entered the vascular system and been transported to the liver via the blood circulation. At 72h, AuNPs were seen further away from sinusoids, being identified in and around hepatocytes. The AuNPs also appear to have been phagocytosed by Kupffer cells within the sinusoid as seen in Figure 3D, where a discrete cell body was visualised containing copious numbers of AuNP clusters.

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