title: Characterization of interaction of magnetic nanoparticles with breast cancer cells.
abstract: BACKGROUND
  Different superparamagnetic iron oxide nanoparticles have been tested for their potential use in cancer treatment, as they enter into cells with high effectiveness, do not induce cytotoxicity, and are retained for relatively long periods of time inside the cells. We have analyzed the interaction, internalization and biocompatibility of dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles with an average diameter of 15 nm and negative surface charge in MCF-7 breast cancer cells.
  
  
  RESULTS
  Cells were incubated with dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles for different time intervals, ranging from 0.5 to 72 h. These nanoparticles showed efficient internalization and relatively slow clearance. Time-dependent uptake studies demonstrated the maximum accumulation of dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles after 24 h of incubation, and afterwards they were slowly removed from cells. Superparamagnetic iron oxide nanoparticles were internalized by energy dependent endocytosis and localized in endosomes. Transmission electron microscopy studies showed macropinocytosis uptake and clathrin-mediated internalization depending on the nanoparticles aggregate size. MCF-7 cells accumulated these nanoparticles without any significant effect on cell morphology, cytoskeleton organization, cell cycle distribution, reactive oxygen species generation and cell viability, showing a similar behavior to untreated control cells.
  
  
  CONCLUSIONS
  All these findings indicate that dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles have excellent properties in terms of efficiency and biocompatibility for application to target breast cancer cells.
authors.affiliation: Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain. macarena.calero@uam.es.|Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Cantoblanco, 28049, Madrid, Spain. macarena.calero@uam.es.
authors.forename: Macarena
authors.initials: M
authors.lastname: Calero
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049, Madrid, Spain. mchiappi@cnb.csic.es.
authors.forename: Michele
authors.initials: M
authors.lastname: Chiappi
authors.affiliation: Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain. ana.lazaro@uam.es.|Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Cantoblanco, 28049, Madrid, Spain. ana.lazaro@uam.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Lazaro-Carrillo
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049, Madrid, Spain. mjrguez@cnb.csic.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Rodríguez
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049, Madrid, Spain. fjchichon@cnb.csic.es.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Chichón
authors.affiliation: Department of Clinical Medicine, Trinity Centre for Health Science, James's Street, Dublin, 8, Ireland. crosbiek@tcd.ie.
authors.forename: Kieran
authors.initials: K
authors.lastname: Crosbie-Staunton
authors.affiliation: Department of Clinical Medicine, Trinity Centre for Health Science, James's Street, Dublin, 8, Ireland. prinamea@tcd.ie.|Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), and AMBER Centre, Trinity College Dublin, College Green, Dublin, 2, Ireland. prinamea@tcd.ie.
authors.forename: Adriele
authors.initials: A
authors.lastname: Prina-Mello
authors.affiliation: Department of Clinical Medicine, Trinity Centre for Health Science, James's Street, Dublin, 8, Ireland. yvolkov@tcd.ie.|Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), and AMBER Centre, Trinity College Dublin, College Green, Dublin, 2, Ireland. yvolkov@tcd.ie.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
authors.affiliation: Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain. angeles.villanueva@uam.es.|Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Cantoblanco, 28049, Madrid, Spain. angeles.villanueva@uam.es.
authors.forename: Angeles
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Department of Macromolecular Structure, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049, Madrid, Spain. jlcarras@cnb.csic.es.|Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Cantoblanco, 28049, Madrid, Spain. jlcarras@cnb.csic.es.
authors.forename: José L
authors.initials: JL
authors.lastname: Carrascosa
mesh_terms: D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D010873:Pinocytosis; D004113:Succimer / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020099:Coated Materials, Biocompatible; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D004113:Succimer