Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles.

In general, gold nanoparticles are recognized as being as nontoxic. Still, there have been some reports on their toxicity, which has been shown to depend on the physical dimension, surface chemistry, and shape of the nanoparticles. In this study, we carry out an in vivo toxicity study using 13 nm-sized gold nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG-coated gold nanoparticles were seen to induce acute inflammation and apoptosis in the liver. These nanoparticles were found to accumulate in the liver and spleen for up to 7 days after injection and to have long blood circulation times. In addition, transmission electron microscopy showed that numerous cytoplasmic vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG-coated gold nanoparticles may have important clinical implications regarding the safety issue as PEG-coated gold nanoparticles are widely used in biomedical applications.

[1]  Wei Qian,et al.  The effect of plasmon field on the coherent lattice phonon oscillation in electron-beam fabricated gold nanoparticle pairs. , 2007, Nano letters.

[2]  B Merchant,et al.  Gold, the noble metal and the paradoxes of its toxicology. , 1998, Biologicals : journal of the International Association of Biological Standardization.

[3]  M. Grunze,et al.  Factors that determine the protein resistance of oligoether self-assembled monolayers --internal hydrophilicity, terminal hydrophilicity, and lateral packing density. , 2003, Journal of the American Chemical Society.

[4]  Alexander M. Klibanov,et al.  Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Kerman,et al.  Electrochemical detection of kinase-catalyzed thiophosphorylation using gold nanoparticles. , 2007, Chemical communications.

[6]  Uri Banin,et al.  Visible light-induced charge retention and photocatalysis with hybrid CdSe-Au nanodumbbells. , 2008, Nano letters.

[7]  Jesus M de la Fuente,et al.  Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus. , 2005, Bioconjugate chemistry.

[8]  C. Mirkin,et al.  Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins , 2003, Science.

[9]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

[10]  Tsuneji Nagai,et al.  Superparamagnetic iron oxide nanoparticles stabilized by alginate: pharmacokinetics, tissue distribution, and applications in detecting liver cancers. , 2008, International journal of pharmaceutics.

[11]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[12]  Sung Jun Kim,et al.  Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles. , 2007, Toxicology letters.

[13]  Abraham Ulman,et al.  Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. , 2006, Small.

[14]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[15]  E. Zubarev,et al.  Paclitaxel-functionalized gold nanoparticles. , 2007, Journal of the American Chemical Society.

[16]  May D. Wang,et al.  In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags , 2008, Nature Biotechnology.

[17]  Sabine Neuss,et al.  Size-dependent cytotoxicity of gold nanoparticles. , 2007, Small.

[18]  Warren C W Chan,et al.  Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. , 2007, Nano letters.

[19]  M. Dobrovolskaia,et al.  Immunological properties of engineered nanomaterials , 2007, Nature Nanotechnology.

[20]  A. Curtis,et al.  Notice of Violation of IEEE Publication Principles Nuclear Localization of HIV-1 Tat Functionalized Gold Nanoparticles , 2007 .

[21]  Kwon-Ha Yoon,et al.  Colloidal Gold Nanoparticles as a Blood-Pool Contrast Agent for X-ray Computed Tomography in Mice , 2007, Investigative radiology.

[22]  R. Shukla,et al.  Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[23]  Steven A Curley,et al.  Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence , 2006, Proceedings of the National Academy of Sciences.

[24]  A. Curtis,et al.  Nuclear localization of HIV-1 tat functionalized gold nanoparticles. , 2007, IEEE transactions on nanobioscience.

[25]  G. Frens.  Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions , 1973 .

[26]  Scott E McNeil,et al.  Nanotechnology safety concerns revisited. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.