title: Investigating the toxic effects of iron oxide nanoparticles.
abstract: 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.
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Soenen
authors.forename: Marcel
authors.initials: M
authors.lastname: De Cuyper
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.forename: Kevin
authors.initials: K
authors.lastname: Braeckmans
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057075:Enzyme Assays; D005290:Ferric Compounds / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D061251:Primary Cell Culture; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C000499:ferric oxide; D007770:L-Lactate Dehydrogenase