Investigating the toxic effects of iron oxide nanoparticles.

The use of iron oxide nanoparticles (IONPs) in biomedical research is steadily increasing, leading to the rapid development of novel IONP types and an increased exposure of cultured cells to a wide variety of IONPs. Due to the large variation in incubation conditions, IONP characteristics, and cell types studied, it is still unclear whether IONPs are generally safe or should be used with caution. During the past years, several contradictory observations have been reported, which highlight the great need for a more thorough understanding of cell-IONP interactions. To improve our knowledge in this field, there is a great need for standardized protocols and toxicity assays, that would allow to directly compare the cytotoxic potential of any IONP type with previously screened particles. Here, several approaches are described that allow to rapidly but thoroughly address several parameters which are of great impact for IONP-induced toxicity. These assays focus on acute cytotoxicity, induction of reactive oxygen species, measuring the amount of cell-associated iron, assessing cell morphology, cell proliferation, cell functionality, and possible pH-induced or intracellular IONP degradation. Together, these assays may form the basis for any detailed study on IONP cytotoxicity.

[1]  Hon-Man Liu,et al.  The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. , 2010, Toxicology and applied pharmacology.

[2]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[3]  B. Weidenfeller,et al.  Thermal, electrical and magnetic studies of magnetite filled polyurethane shape memory polymers , 2007 .

[4]  T. Dresselaers,et al.  Cell labeling and tracking for experimental models using magnetic resonance imaging. , 2009, Methods.

[5]  Vincent M Rotello,et al.  Functionalized gold nanoparticles for drug delivery. , 2007, Nanomedicine.

[6]  Sungho Jin,et al.  Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. , 2007, Biomaterials.

[7]  K. Neoh,et al.  Cellular response to magnetic nanoparticles "PEGylated" via surface-initiated atom transfer radical polymerization. , 2006, Biomacromolecules.

[8]  L. Greene,et al.  Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Soenen,et al.  Addressing the problem of cationic lipid-mediated toxicity: the magnetoliposome model. , 2009, Biomaterials.

[10]  Jerry S. H. Lee,et al.  Magnetic nanoparticles in MR imaging and drug delivery. , 2008, Advanced drug delivery reviews.

[11]  S. Nie,et al.  Luminescent quantum dots for multiplexed biological detection and imaging. , 2002, Current opinion in biotechnology.

[12]  A. Arbab,et al.  Labeling of cells with ferumoxides–protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells , 2005, NMR in biomedicine.

[13]  E Meijering,et al.  Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images , 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[14]  Ajay Kumar Gupta,et al.  Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles. , 2005, Biomaterials.

[15]  A. Arbab,et al.  Expression of transferrin receptor and ferritin following ferumoxides–protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging , 2006, NMR in biomedicine.

[16]  S. Soenen,et al.  Magnetoliposomes: versatile innovative nanocolloids for use in biotechnology and biomedicine. , 2009, Nanomedicine.

[17]  S. Soenen,et al.  Cationic magnetoliposomes. , 2010, Methods in molecular biology.

[18]  Uwe Himmelreich,et al.  Cytotoxic effects of iron oxide nanoparticles and implications for safety in cell labelling. , 2011, Biomaterials.

[19]  K. Braeckmans,et al.  The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes. , 2009, Biomaterials.

[20]  Bryce J Marquis,et al.  Toxicity of therapeutic nanoparticles. , 2009, Nanomedicine.

[21]  Alison Elder,et al.  Correlating physico-chemical with toxicological properties of nanoparticles: the present and the future. , 2010, ACS nano.

[22]  Nastassja A. Lewinski,et al.  Cytotoxicity of nanoparticles. , 2008, Small.

[23]  Alan P Koretsky,et al.  Sizing it up: Cellular MRI using micron‐sized iron oxide particles , 2005, Magnetic resonance in medicine.

[24]  B. Tycko,et al.  Rapid acidification of endocytic vesicles containing α 2-macroglobulin , 1982, Cell.

[25]  S. Soenen,et al.  Assessing cytotoxicity of (iron oxide-based) nanoparticles: an overview of different methods exemplified with cationic magnetoliposomes. , 2009, Contrast media & molecular imaging.

[26]  John J. Schlager,et al.  Toxicity Evaluation for Safe Use of Nanomaterials: Recent Achievements and Technical Challenges , 2009 .

[27]  Bobbi K Lewis,et al.  A model of lysosomal metabolism of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles: implications for cellular magnetic resonance imaging , 2005, NMR in biomedicine.

[28]  Heather Kalish,et al.  Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. , 2003, Radiology.

[29]  S. Soenen,et al.  How to assess cytotoxicity of (iron oxide-based) nanoparticles: a technical note using cationic magnetoliposomes. , 2011, Contrast media & molecular imaging.

[30]  Brahim Lounis,et al.  Cathepsin L digestion of nanobioconjugates upon endocytosis. , 2009, ACS nano.

[31]  Wolfgang J. Parak,et al.  Cellular toxicity of inorganic nanoparticles: Common aspects and guidelines for improved nanotoxicity evaluation , 2011 .

[32]  S. Soenen,et al.  Optimal Conditions for Labelling of 3T3 Fibroblasts with Magnetoliposomes without Affecting Cellular Viability , 2007, Chembiochem : a European journal of chemical biology.

[33]  P. Walczak,et al.  Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: The case of the Shiverer dysmyelinated mouse brain , 2007, Magnetic resonance in medicine.

[34]  C. Claussen,et al.  Transferrin receptor upregulation: in vitro labeling of rat mesenchymal stem cells with superparamagnetic iron oxide. , 2007, Radiology.

[35]  S. Soenen,et al.  Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects. , 2010, Nanomedicine.

[36]  Isabelle Raynal,et al.  Macrophage Endocytosis of Superparamagnetic Iron Oxide Nanoparticles: Mechanisms and Comparison of Ferumoxides and Ferumoxtran-10 , 2004, Investigative radiology.

[37]  Tilman Grune,et al.  Iron oxide particles for molecular magnetic resonance imaging cause transient oxidative stress in rat macrophages. , 2004, Free radical biology & medicine.

[38]  B. Tycko,et al.  Rapid acidification of endocytic vesicles containing alpha 2-macroglobulin. , 1982, Cell.

[39]  T. R. Pisanic,et al.  Intracellular nanoparticle coating stability determines nanoparticle diagnostics efficacy and cell functionality. , 2010, Small.

[40]  R. Hebbel,et al.  Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor. , 2006, Blood.

[41]  Stefaan C De Smedt,et al.  High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling. , 2010, Small.