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

Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, People's Republic of China.
International Journal of Nanomedicine (Impact Factor: 4.2). 01/2011; 6:2071-81. DOI: 10.2147/IJN.S21657
Source: PubMed

ABSTRACT 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.
Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 μg/kg over 28 days.
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.
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.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Through increased awareness and improved diagnostics, microsporidiosis has now been identified in a broader range of human populations; however current therapies are inconsistently effective. Recently, probiotics were determined as means for the control of intestinal parasitic infections through their secretory products; bacteriocins. This is the first study on the effect of bacteriocin produced by Lactobacillus acidophilus CH1 bacteriocin, with or without gold nanoparticles (Au-NPs), against intestinal microsporidiosis in immunosuppressed mice. Fecal and intestinal spore loads, besides viability, extrusion and infectivity of spores from treated animals were assessed. Results showed that the anti-microsporidal effects of bacteriocin were significantly potent. This efficiency was further potentiated upon conjugating bacteriocins with Au-NPs, as it induced a strikingly sustained reduction in fecal spore shedding after cessation of therapy by one week (94.26%). Furthermore, reduction in intestinal spore load was highest in bacteriocin/Au-NPs-inoculated mice (89.7%) followed by bacteriocin-inoculated group (73.5%). Spores encountered from stool of bacteriocin/Au-NPs group showed 92.4% viability, versus 93.7% in bacteriocin group. Spore extrusion and infectivity were most inhibited by exposure to bacteriocin/Au-NPs. Safety of bacteriocin/Au-NPs was also verified. Thus, considering the results of the present work, Lactobacillus acidophilus CH1-derived bacteriocin can present a powerful safe therapy against intestinal microsporidiosis.
    Experimental Parasitology 06/2014; · 1.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Surface chemistry plays an important role in gold nanoparticles(AuNPs) stability and biocompatibility, which are crucial for their successful implementation into the clinical setting. We evaluated short-(30min) and long-term(28days) biodistribution and toxicity of ~20nm citrate- and pentapeptide CALNN-coated AuNPs after a single intravenous injection (~0.7mg Au/Kg) in rats. The pattern of AuNPs distribution in Cit- and CALNN-AuNPs-injected rats was very similar in the assessed time-points. Both AuNPs were quickly removed from the bloodstream and preferentially accumulated in the liver. At 28days post-injection, liver remained the main accumulation site but at significantly lower levels compared to those found at 30min. Spleen atrophy and hematological findings compatible with mild anaemia were observed in CALNN-AuNPs-administered rats. Under our experimental conditions, surface coating had more impact on toxicity rather than on biodistribution of the AuNPs. Further improvements in the design of capping peptides need to be done to increase biomedical applicability of peptide-coated AuNPs.
    Nanomedicine Nanotechnology Biology and Medicine 06/2014; · 5.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra-small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Although immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using systemic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene delivery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.
    Advances in Molecular Imaging 10/2012; 2(4):31-37.

Full-text (2 Sources)

Available from
May 22, 2014