title: Cell compatibility of a maghemite/polymer biomedical nanoplatform.
abstract: We are reporting the cytocompatibility and cellular fate of an iron oxide/polymer nanoplatform (IONP) in its most basic formulation, using both mesenchymal (vascular smooth muscle cells, VSMC), and epithelial (opossum kidney, OK) cells. The cytotoxicity and cell internalization of the nanoplatform has been evaluated in relation to time of exposure and concentration of different components. A series of samples with different iron oxide nanoparticle, sizes, hydrodynamic sizes and iron/polymer ratio have been examined. In all cases cytotoxicity is low, and it is mostly determined by the internalization rate, being higher in VSMC than in OK cells. The mean lethal dose has a very narrow threshold, and necrosis is the only cell death type. IONP uptake shows little incidence on oxidative stress, and inflammasome activation is only observed with the smaller IONP at high concentration. The internalization rate in VSMC is determined by the polymer concentration exclusively. In OK cells, internalization rate seems to increase with decreasing hydrodynamic size. Internalization occurs through clathrin-dependent endocytosis, as it is prevented by potassium depletion and chlorpromazine. IONP are directed and accumulated in lysosomes. Under IONP overload, lysosomal dysfunction would cause cell death using concentrations that are hardly achieved in vivo.
authors.affiliation: Instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza, C/Pedro Cerbuna 10, 50009 Zaragoza, Spain; Department of Toxicology, University of Zaragoza, Veterinary Faculty, C/Miguel Servet 177, E50013 Zaragoza, Spain.
authors.forename: Lamiaa M A
authors.initials: LM
authors.lastname: Ali
authors.affiliation: Instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza, C/Pedro Cerbuna 10, 50009 Zaragoza, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Piñol
authors.affiliation: Department of Toxicology, University of Zaragoza, Veterinary Faculty, C/Miguel Servet 177, E50013 Zaragoza, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Villa-Bellosta
authors.affiliation: Instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza, C/Pedro Cerbuna 10, 50009 Zaragoza, Spain.
authors.forename: Lierni
authors.initials: L
authors.lastname: Gabilondo
authors.affiliation: Instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza, C/Pedro Cerbuna 10, 50009 Zaragoza, Spain. Electronic address: amillan@unizar.es.
authors.forename: Angel
authors.initials: A
authors.lastname: Millán
authors.affiliation: Instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza, C/Pedro Cerbuna 10, 50009 Zaragoza, Spain. Electronic address: palacio@unizar.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Palacio
authors.affiliation: Department of Toxicology, University of Zaragoza, Veterinary Faculty, C/Miguel Servet 177, E50013 Zaragoza, Spain. Electronic address: sorribas@unizar.es.
authors.forename: Victor
authors.initials: V
authors.lastname: Sorribas
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004705:Endocytosis; D005290:Ferric Compounds / Q000633:toxicity*; D008247:Lysosomes / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D011108:Polymers / Q000633:toxicity*; D051381:Rats
chemical_list: D005290:Ferric Compounds; D011108:Polymers; C000499:ferric oxide
keywords: Cell internalization; Cytotoxicity; Iron oxide; Nanoparticles; Subcellular localization