Cytotoxic effects of iron oxide nanoparticles and implications for safety in cell labelling

• Published in: Biomaterials Vol. 32; no. 1; pp. 195 - 205
• Main Authors: Soenen, Stefaan J.H, Himmelreich, Uwe, Nuytten, Nele, De Cuyper, Marcel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-01-2011
• Subjects: (Iron oxide) nanoparticle; Advanced Basic Science; agar; Animals; Biomedical materials; biomedical research; blood; Cell Cycle - drug effects; Cell Death - drug effects; Cell labelling; Cell Movement - drug effects; cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemical Phenomena - drug effects; Contrast Media - pharmacology; cultured cells; cytoskeleton; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Cytotoxicity; Dentistry; dextran; Endocytosis - drug effects; endothelial cells; Ferric Compounds - toxicity; Focal Adhesions - drug effects; Focal Adhesions - metabolism; homeostasis; Homeostasis - drug effects; Humans; in vitro studies; Intracellular Space - drug effects; Intracellular Space - metabolism; iron; Iron - metabolism; iron oxides; labeling techniques; lipids; Magnetic Resonance Imaging; Magnetoliposome; nanoparticles; Nanoparticles - toxicity; PC12 Cells; Rats; reactive oxygen species; Reactive Oxygen Species - metabolism; Staining and Labeling - methods; stem cells; viability; Cytotoxicity; Biomedical materials; (Iron oxide) nanoparticle; Magnetoliposome; Cell labelling
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.08.075

The in vitro labelling of cultured cells with iron oxide nanoparticles (NPs) is a frequent practice in biomedical research. To date, the potential cytotoxicity of these particles remains an issue of debate. In the present study, 4 different NP types (dextran-coated Endorem, carboxydextran-coated Resovist, lipid-coated magnetoliposomes (MLs) and citrate-coated very small iron oxide particles (VSOP)) are tested on a variety of cell types, being C17.2 neural progenitor cells, PC12 rat pheochromocytoma cells and human blood outgrowth endothelial cells. Using different NP concentrations, the effect of the NPs on cell morphology, cytoskeleton, proliferation, reactive oxygen species, functionality, viability and cellular homeostasis is investigated. Through a systematic study, the safe concentrations for every particle type are determined, showing that MLs can lead up to 67.37 ± 5.98 pg Fe/cell whereas VSOP are the most toxic particles and only reach 18.65 ± 2.07 pg Fe/cell. Using these concentrations, it is shown that for MRI up to 500 cells/μl labelled with VSOP are required to efficiently visualize in an agar phantom in contrast to only 50 cells/μl for MLs and 200 cells/μl for Endorem and Resovist. These results highlight the importance of in-depth cytotoxic evaluation of cell labelling studies as at non-toxic concentrations, some particles appear to be less suitable for the MR visualization of labelled cells.