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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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Abdominal adipose tissue distribution of AuNPs following intraperitoneal injection into mice.Scanning electron microscopy (SEM) images of abdominal adipose tissue in (A) control mouse and (B) AuNP-injected mouse at 24 h (Mag 2.01K x). (C, D) Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) images of abdominal adipose tissue at 24 h. (C) displaying the carbon present throughout the tissue sample, of medium to low signal intensity, (D) displays the gold present throughout the tissue sample, concentrated around the periphery of a portion of tissue within the section, of medium to high intensity. The strength of the signal transmitted for a selected element is represented by a corresponding colour, blue signifying the lowest signal strength and red the highest.
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pone-0058208-g001: Abdominal adipose tissue distribution of AuNPs following intraperitoneal injection into mice.Scanning electron microscopy (SEM) images of abdominal adipose tissue in (A) control mouse and (B) AuNP-injected mouse at 24 h (Mag 2.01K x). (C, D) Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) images of abdominal adipose tissue at 24 h. (C) displaying the carbon present throughout the tissue sample, of medium to low signal intensity, (D) displays the gold present throughout the tissue sample, concentrated around the periphery of a portion of tissue within the section, of medium to high intensity. The strength of the signal transmitted for a selected element is represented by a corresponding colour, blue signifying the lowest signal strength and red the highest.

Mentions: From the SEM images, AuNPs can be clearly identified from the dark background of fat tissue cells (Figure 1B), as the AuNPs appear bright white in contrast to the tissue, which was not seen in the control mice (Figure 1A). In the images, AuNPs appear as spheres and clusters in the tissue. SEM imaging revealed that in the abdominal fat, AuNPs were located predominantly within the periphery of the fat tissue, few clusters were seen further into the tissue between the adipocytes at 24 h post AuNPs-injection (Figure 1B). No AuNP-like substance was observed within the tissue of control mice. The presence of AuNPs within tissues was further confirmed by using LA-ICPMS. This was done using a section of abdominal fat from an AuNP injected mouse, at 24 h post-injection (Figure 1C, D). Figure 1C showed the carbon present throughout the fat tissue, suggesting the organic nature of the tissue. The colour spectrum representing varying signal strength is shown in Figure 1D, with yellow to red indicating the presence of gold. In Figure 1D, it is clearly evident that the accumulation of AuNPs in the periphery of the fat tissue, which represents a similar pattern to that observed in the SEM image (Figure 1B). The intensity of the signal in this region indicates that the amount of AuNPs present is substantial. SEM scanning showed that AuNPs were only found in the abdominal fat tissues and the liver. There were no AuNPs present in the other major organs investigated in this study, including brain, kidney and heart (images not shown).


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)

Abdominal adipose tissue distribution of AuNPs following intraperitoneal injection into mice.Scanning electron microscopy (SEM) images of abdominal adipose tissue in (A) control mouse and (B) AuNP-injected mouse at 24 h (Mag 2.01K x). (C, D) Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) images of abdominal adipose tissue at 24 h. (C) displaying the carbon present throughout the tissue sample, of medium to low signal intensity, (D) displays the gold present throughout the tissue sample, concentrated around the periphery of a portion of tissue within the section, of medium to high intensity. The strength of the signal transmitted for a selected element is represented by a corresponding colour, blue signifying the lowest signal strength and red the highest.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585265&req=5

pone-0058208-g001: Abdominal adipose tissue distribution of AuNPs following intraperitoneal injection into mice.Scanning electron microscopy (SEM) images of abdominal adipose tissue in (A) control mouse and (B) AuNP-injected mouse at 24 h (Mag 2.01K x). (C, D) Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) images of abdominal adipose tissue at 24 h. (C) displaying the carbon present throughout the tissue sample, of medium to low signal intensity, (D) displays the gold present throughout the tissue sample, concentrated around the periphery of a portion of tissue within the section, of medium to high intensity. The strength of the signal transmitted for a selected element is represented by a corresponding colour, blue signifying the lowest signal strength and red the highest.
Mentions: From the SEM images, AuNPs can be clearly identified from the dark background of fat tissue cells (Figure 1B), as the AuNPs appear bright white in contrast to the tissue, which was not seen in the control mice (Figure 1A). In the images, AuNPs appear as spheres and clusters in the tissue. SEM imaging revealed that in the abdominal fat, AuNPs were located predominantly within the periphery of the fat tissue, few clusters were seen further into the tissue between the adipocytes at 24 h post AuNPs-injection (Figure 1B). No AuNP-like substance was observed within the tissue of control mice. The presence of AuNPs within tissues was further confirmed by using LA-ICPMS. This was done using a section of abdominal fat from an AuNP injected mouse, at 24 h post-injection (Figure 1C, D). Figure 1C showed the carbon present throughout the fat tissue, suggesting the organic nature of the tissue. The colour spectrum representing varying signal strength is shown in Figure 1D, with yellow to red indicating the presence of gold. In Figure 1D, it is clearly evident that the accumulation of AuNPs in the periphery of the fat tissue, which represents a similar pattern to that observed in the SEM image (Figure 1B). The intensity of the signal in this region indicates that the amount of AuNPs present is substantial. SEM scanning showed that AuNPs were only found in the abdominal fat tissues and the liver. There were no AuNPs present in the other major organs investigated in this study, including brain, kidney and heart (images not shown).

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