Embryotoxicity of cobalt ferrite and gold nanoparticles: a first in vitro approach.

Nanoparticles (NPs) are emerging as promising biomedical tools thanks to their peculiar characteristics. Our purpose was to investigate the embryotoxicity of cobalt ferrite and gold NPs through the Embryonic Stem Cell Test (EST). The EST is an in vitro standard assay, which permits to classify substances as strongly, weakly or non-embryotoxic. Due to the particular physical-chemical nature of nanoparticles, we introduced a modification to the standard protocol exposing the Embryonic Stem Cells (ES-D3) to nanoparticles only during the first 5 days of the assay. Moreover, we proposed a method to discriminate and compare the embryotoxicity of the substances within the weakly embryotoxic range. Our ID(50) results permit to classify cobalt ferrite nanoparticles coated with gold and silanes as non-embryotoxic. The remaining nanoparticles have been classified as weakly embryotoxic in this decreasing order: gold salt (HAuCl(4).3H(2)O)>cobalt ferrite salt (CoFe(2)O(4))>cobalt ferrite nanoparticles coated with silanes (Si-CoFe)>gold nanoparticles coated with hyaluronic acid (HA-Au).

[1]  M. A. Croce,et al.  Hyaluronan affects protein and collagen synthesis by in vitro human skin fibroblasts. , 2001, Tissue & cell.

[2]  Aldert H Piersma,et al.  In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. , 2009, Toxicology and applied pharmacology.

[3]  Kyoung-Nam Kim,et al.  Cytotoxicity of ferrite particles by MTT and agar diffusion methods for hyperthermic application , 2005 .

[4]  Wolfgang J Parak,et al.  Laser-induced release of encapsulated materials inside living cells. , 2006, Angewandte Chemie.

[5]  J. Piek,et al.  Hyaluronic acid: targeting immune modulatory components of the extracellular matrix in atherosclerosis. , 2008, Current medicinal chemistry.

[6]  Susanne Bremer,et al.  Validation of the Embryonic Stem Cell Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests , 2004, Alternatives to laboratory animals : ATLA.

[7]  J. Pennings,et al.  Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells. , 2010, Toxicology and applied pharmacology.

[8]  A. Piersma,et al.  Disentangling cellular proliferation and differentiation in the embryonic stem cell test, and its impact on the experimental protocol. , 2009, Reproductive toxicology.

[9]  W. Hoefnagels,et al.  No Effect of One-Year Treatment with Indomethacin on Alzheimer's Disease Progression: A Randomized Controlled Trial , 2008, PloS one.

[10]  Katharina Landfester,et al.  Interaction of nanoparticles with cells. , 2009, Biomacromolecules.

[11]  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.

[12]  O. Flint,et al.  An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. , 1984, Toxicology and applied pharmacology.

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

[14]  M. Mummert Immunologic roles of hyaluronan , 2005, Immunologic research.

[15]  Vincent M Rotello,et al.  Gold nanoparticles in delivery applications. , 2008, Advanced drug delivery reviews.

[16]  M. Reigosa,et al.  Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. , 2010, Journal of hazardous materials.

[17]  H. Spielmann,et al.  The embryonic stem cell test (EST), an in vitro embryotoxicity test using two permanent mouse cell lines : 3T3 fibroblasts and embryonic stem cells , 1997 .

[18]  A. Ceylan,et al.  Synthesis and magnetic properties of cobalt ferrite (CoFe2O4) nanoparticles prepared by wet chemical route , 2006, cond-mat/0606631.

[19]  P. Jain,et al.  Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy. , 2007, Nanomedicine.

[20]  Akiko Yamamoto,et al.  Cytotoxicity evaluation of ceramic particles of different sizes and shapes. , 2004, Journal of biomedical materials research. Part A.

[21]  R Kemler,et al.  The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. , 1985, Journal of embryology and experimental morphology.

[22]  K. Seung,et al.  Magnetic resonance tracking of multifunctional nanoparticle-labeled mouse mesenchymal stem cells in a mouse model of myocardial infarction , 2009 .

[23]  W. Patton,et al.  Development of mammalian embryos exposed to mixed-size nanoparticles. , 2005, Clinical and experimental obstetrics & gynecology.

[24]  Roland Buesen,et al.  Improvement of an in vitro stem cell assay for developmental toxicity: the use of molecular endpoints in the embryonic stem cell test. , 2004, Reproductive toxicology.

[25]  Suresh Valiyaveettil,et al.  DNA damage and p53-mediated growth arrest in human cells treated with platinum nanoparticles. , 2010, Nanomedicine.

[26]  C. Maxwell,et al.  Hyaluronan and hyaluronan synthases: potential therapeutic targets in cancer. , 2005, Current drug targets. Cardiovascular & haematological disorders.

[27]  H. Stuhlmann,et al.  Use of developmental marker genes to define temporal and spatial patterns of differentiation during embryoid body formation. , 1999, The Journal of experimental zoology.

[28]  H Raabe,et al.  Prevalidation of the Embryonic Stem Cell Test (EST)-A New In Vitro Embryotoxicity Test. , 1999, Toxicology in vitro : an international journal published in association with BIBRA.