title: Nanoclusters of iron oxide: effect of core composition on structure, biocompatibility, and cell labeling efficacy.
abstract: Inorganic nanocrystals have a variety of applications in medicine. They may serve as contrast agents, therapeutics, and for in vitro diagnostics. Frequently, the synthesis route yields hydrophobically capped nanocrystals, which necessitates their subsequent coating to render a water-soluble and biocompatible probe. Biocompatibility is crucial for cellular imaging applications, which require large quantities of diagnostically active nanoparticles to be loaded into cells. We have previously reported the design and synthesis of a fluorescent and magnetic resonance imaging-detectable core-shell nanoparticle that encapsulates hydrophobically coated iron oxide nanocrystals. The core of soybean oil and iron oxide is covered by a shell mixture of phospholipids, some of which contained polyethylene glycol. Despite the biocompatibility of these components, we hypothesize that we can improve this formulation with respect to in vitro toxicity. To this aim, we measured the effect of six different core compositions on nanoparticle structure, cell labeling efficacy, and cell viability, as well as cell tracking potential. We methodically investigated the causes of toxicity and conclude that, even when combining biocompatible materials, the resulting formulation is not guaranteed to be biocompatible.
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht , Utrecht, The Netherlands.
authors.forename: Geralda A F
authors.initials: GA
authors.lastname: van Tilborg
authors.forename: David P
authors.initials: DP
authors.lastname: Cormode
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jarzyna
authors.forename: Annette
authors.initials: A
authors.lastname: van der Toorn
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: van der Pol
authors.forename: Louis
authors.initials: L
authors.lastname: van Bloois
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000032:analysis / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000032:analysis* / Q000633:toxicity; D005290:Ferric Compounds / Q000032:analysis* / Q000633:toxicity; D005456:Fluorescent Dyes / Q000032:analysis / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000032:analysis* / Q000633:toxicity / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000032:analysis / Q000633:toxicity
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D005290:Ferric Compounds; D005456:Fluorescent Dyes; C000499:ferric oxide; D011092:Polyethylene Glycols