Intracellular uptake and toxicity of Ag and CuO nanoparticles: a comparison between nanoparticles and their corresponding metal ions.

UNLABELLED An increased understanding of nanoparticle toxicity and its impact on human health is essential to enable a safe use of nanoparticles in our society. The aim of this study is to investigate the role of a Trojan horse type mechanism for the toxicity of Ag-nano and CuO-nano particles and their corresponding metal ionic species (using CuCl2 and AgNO3 ), i.e., the importance of the solid particle to mediate cellular uptake and subsequent release of toxic species inside the cell. The human lung cell lines A549 and BEAS-2B are used and cell death/membrane integrity and DNA damage are investigated by means of trypan blue staining and the comet assay, respectively. Chemical analysis of the cellular dose of copper and silver is performed using atomic absorption spectroscopy. Furthermore, transmission electron microscopy, laser scanning confocal microscopy, and confocal Raman microscopy are employed to study cellular uptake and particle-cell interactions. The results confirm a high uptake of CuO-nano and Ag-nano compared to no, or low, uptake of the soluble salts. CuO-nano induces both cell death and DNA damage whereas CuCl2 induces no toxicity. The opposite is observed for silver, where Ag-nano does not cause any toxicity, whereas AgNO3 induces a high level of cell death. IN CONCLUSION CuO-nano toxicity is predominantly mediated by intracellular uptake and subsequent release of copper ions, whereas no toxicity is observed for Ag-nano due to low release of silver ions within short time periods.

[1]  Alexander M Seifalian,et al.  Nanosilver as a new generation of nanoproduct in biomedical applications. , 2010, Trends in biotechnology.

[2]  Herman Autrup,et al.  Toxicity of silver nanoparticles - nanoparticle or silver ion? , 2012, Toxicology letters.

[3]  Lennart Möller,et al.  Effect of sonication and serum proteins on copper release from copper nanoparticles and the toxicity towards lung epithelial cells , 2011, Nanotoxicology.

[4]  M. Klein,et al.  Enhanced Raman scattering from adsorbates on metal films in ultra-high vacuum , 1981 .

[5]  F. Rossi,et al.  Genotoxicity and morphological transformation induced by cobalt nanoparticles and cobalt chloride: an in vitro study in Balb/3T3 mouse fibroblasts. , 2009, Mutagenesis.

[6]  Ying Liu,et al.  Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. , 2011, Small.

[7]  N. Pante,et al.  Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. , 2002, Molecular biology of the cell.

[8]  A. Gedanken,et al.  Understanding the antibacterial mechanism of CuO nanoparticles: revealing the route of induced oxidative stress. , 2012, Small.

[9]  R. Amal,et al.  Cytotoxic origin of copper(II) oxide nanoparticles: comparative studies with micron-sized particles, leachate, and metal salts. , 2011, ACS nano.

[10]  K. L. de Mesy Bentley,et al.  Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response. , 2009, Nanotoxicology.

[11]  B. Sexton,et al.  The adsorption and reaction of H2O on clean and oxygen covered Ag(110) , 1981 .

[12]  A Study of Glutathione Molecules Adsorbed on Silver Surfaces under Different Chemical Environments by Surface-Enhanced Raman Scattering in Combination with the Heat-Induced Sensing Method , 2010, Applied spectroscopy.

[13]  E Sabbioni,et al.  Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro. , 2008, Mutagenesis.

[14]  A. Talari,et al.  Raman Spectroscopy of Biological Tissues , 2007 .

[15]  Joseph C. Farmer,et al.  In Situ Raman Spectroscopy of Anodic Films Formed on Copper and Silver in Sodium Hydroxide Solution , 1986 .

[16]  Younan Xia,et al.  The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles. , 2011, Nature nanotechnology.

[17]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[18]  H. Autrup,et al.  Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549 , 2011, Archives of Toxicology.

[19]  S. Tsai,et al.  Compound Cellular Imaging of Laser Scanning Confocal Microscopy by Using Gold Nanoparticles and Dyes , 2008, Sensors.

[20]  K. Kasemets,et al.  Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata. , 2009, The Science of the total environment.

[21]  Peter Wick,et al.  Nanotoxicology: an interdisciplinary challenge. , 2011, Angewandte Chemie.

[22]  Xiaohua Huang,et al.  Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. , 2008, Accounts of chemical research.

[23]  James E Hutchison,et al.  Generation of metal nanoparticles from silver and copper objects: nanoparticle dynamics on surfaces and potential sources of nanoparticles in the environment. , 2011, ACS nano.

[24]  Jin Won Hyun,et al.  Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. , 2011, Toxicology letters.

[25]  Iqbal Ahmad,et al.  Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells. , 2010, Biochemical and biophysical research communications.

[26]  M. Hande,et al.  Cytotoxicity and genotoxicity of silver nanoparticles in human cells. , 2009, ACS nano.

[27]  Andreas Schlicker,et al.  Comparison of manganese oxide nanoparticles and manganese sulfate with regard to oxidative stress, uptake and apoptosis in alveolar epithelial cells. , 2011, Toxicology letters.

[28]  J. Yi,et al.  Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[29]  Yuan Zhang,et al.  Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells. , 2010, Biomaterials.

[30]  H. Karlsson,et al.  The comet assay in nanotoxicology research , 2010, Analytical and bioanalytical chemistry.

[31]  Robert N Grass,et al.  Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress. , 2007, Environmental science & technology.

[32]  Pedro J J Alvarez,et al.  Negligible particle-specific antibacterial activity of silver nanoparticles. , 2012, Nano letters.

[33]  Christofer Leygraf,et al.  Surface characteristics, copper release, and toxicity of nano- and micrometer-sized copper and copper(II) oxide particles: a cross-disciplinary study. , 2009, Small.

[34]  R. Dasari,et al.  Surface-enhanced Raman scattering and biophysics , 2001 .

[35]  H. Karlsson,et al.  Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. , 2008, Chemical research in toxicology.

[36]  S. Sukhishvili,et al.  SERS not to be taken for granted in the presence of oxygen. , 2009, Journal of the American Chemical Society.

[37]  Wendelin J. Stark,et al.  Physico-Chemical Differences Between Particle-and Molecule-Derived Toxicity : Can We Make Inherently Safe Nanoparticles? , 2009 .

[38]  R. Hurt,et al.  Ion release kinetics and particle persistence in aqueous nano-silver colloids. , 2010, Environmental science & technology.