Protracted elimination of gold nanoparticles from mouse liver

Sadauskas, Evaldas; Danscher, Gorm; Stoltenberg, Meredin; Vogel, Ulla; Larsen, Agnete; Wallin, Håkan

doi:10.1016/j.nano.2008.11.002

Cited by 282 publications

(236 citation statements)

References 30 publications

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“…Our data support the notion that bare AuNPs have low ability to escape from the RES [16]. Furthermore, the relatively constant high hepatic Au levels observed during the 24 h indicates that Cit-AuNPs are poorly eliminated, which has also been previously described even for long-term (up to 6 months) studies in rats [6] and mice [8,9,13]. The poor elimination of these AuNPs can be attributed to their relatively large size, since renal excretion would not be expected for NPs with over 5.5 nm average diameter [38].…”

Section: Discussionsupporting

confidence: 90%

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Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Morais

Soares

Duarte

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tSuccessful application of gold nanoparticles (AuNPs) in biomedicine requires extensive safety assessment for which biokinetic studies are crucial.We evaluated the biodistribution of AuNPs ($20 nm) with different surface coatings: citrate, 11-MUA and 3 pentapeptides, CALNN, CALND and CALNS, after i.v. administration to rats (0.6-1 mg Au/kg). Biodistribution was evaluated based on Au tissue content measured by GFAAS.Citrate-AuNPs were rapidly removed from circulation with 60% of the injected dose depositing in the liver. Thirty minutes post-injection, the lungs presented about 6% of the injected dose with levels decreasing to 0.7% at 24 h. Gold levels in the spleen were of 2.6%. After 24 h, liver presented the highest Au level, followed by spleen and blood.A similar biodistribution profile was observed for MUA-coated AuNPs compared to Cit-AuNPs at 24 h post-injection, while significantly higher levels of peptide-capped AuNPs were found in the liver (74-86%) accompanied by a corresponding decrease in blood levels.TEM analysis of liver slices showed AuNPs in Kupffer cells and hepatocytes, trapped inside endosomes. Our data demonstrate that AuNPs are rapidly distributed and that the liver is the preferential accumulation organ. Peptide capping significantly increased hepatic uptake, showing the influence of AuNPs functionalization in biodistribution.

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Section: Discussionsupporting

confidence: 90%

“…Reports on in vivo biodistribution of AuNPs are so far scarce and mainly focused on the kinetics of citrate-coated AuNPs after intravenous (i.v.) injection in rat [6,7] and mouse [8][9][10]. The bioavailability of orally administered AuNPs has also been studied in these animal models [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Morais

Soares

Duarte

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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“…Moreover, the results imply that the spleen is one of the target organs for PEG-coated gold nanoparticles, which is in good agreement with previous work. [32][33][34][35][36][37][38][39][40][41][42]50 The liver and spleen have been described as the two dominant organs for biodistribution and metabolism of gold nanoparticles. [32][33][34][35][36][37][38][39][40][41][42] To quantify the toxicity of the PEG-coated gold nanoparticles, the next important step is assessment of standard hematology and biochemistry, which is very useful for toxicity.…”

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confidence: 99%

Size-dependent in vivo toxicity of PEG-coated gold nanoparticles

Zhang¹,

Wu²,

Shen³

et al. 2011

IJN

389

246

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Background: Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. Methods: Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 µg/kg over 28 days. Results:The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. Conclusion: The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.

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“…It has been reported that nanomaterials are mainly recognized and phagocytosed by macrophages once in the circulation (21,22). The cellular responses induced by nanoparticles are found to be size dependent (23)(24)(25).…”

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confidence: 99%

Size-Dependent Attenuation of TLR9 Signaling by Gold Nanoparticles in Macrophages

Tsai

et al. 2012

The Journal of Immunology

145

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Gold nanoparticles (GNPs), which are generally thought to be bio-inert and non-cytotoxic, have become one of the most ideal nanomaterials for medical applications. Once engulfed by phagocytes, the immunological effects of GNPs are still of concern and require detailed investigation. Therefore, this study explored the immunological significance of GNPs on TLR-mediated innate immunity in murine macrophages. GNP causes specific inhibition of TLR9 (CpG oligodeoxynucleotides; CpG-ODNs) signal in macrophages. The impaired CpG-ODN–induced TNF-α production is GNP concentration- and size-dependent in murine Raw264.7 cells: a GNP of 4 nm in size is more potent than a GNP of 11, 19, 35, or 45 nm in size. Consistent with cytokine inhibition, the CpG-ODN–induced phosphorylation of NF-κB and JNK as well as NF-κB activation are suppressed by GNPs. GNPs accumulate in lysosomes after phagocytosis and also increase TLR9-associated lysosomal cathepsin expression and activities, but this is irrelevant to TLR9 inhibition by GNPs in our studies. In addition, GNPs affected TLR9 translocation in response to CpG-ODNs and to phagosomes. Further exploring how GNPs inhibited TLR9 function, we found that GNPs could bind to high-mobility group box-1 (which is involved in the regulation of TLR9 signaling) inside the lysosomes. The current studies demonstrate that size-dependent inhibition of TLR9 function by GNP may be attributed to its binding to high-mobility group box-1.

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Protracted elimination of gold nanoparticles from mouse liver

Cited by 282 publications

References 30 publications

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Size-dependent in vivo toxicity of PEG-coated gold nanoparticles

Size-Dependent Attenuation of TLR9 Signaling by Gold Nanoparticles in Macrophages

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