title: Effects of iron oxide nanoparticles on biological responses and MR imaging properties in human mammary healthy and breast cancer epithelial cells.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs, diameters >50 nm) have received great attention due to their promising use as magnetic resonance imaging (MRI) contrast agents. In this study, we evaluated the cellular uptake and biological responses in vitro of ultrasmall SPIONs (USPIONs, diameters < 50 nm). We compared the cellular responses between breast epithelia isolated from healthy and breast cancer donors after exposure to carboxy-terminated USPIONs (10 and 30 nm PEG-coated, 10 and 30 nm non-PEG-coated). The particles were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and gel electrophoresis. Cellular interactions with USPIONs were assessed by confocal microscopy and TEM. Cellular uptake of USPIONs was quantified using ICP-MS. Cell viability was measured by MTT and neutral red uptake assays. T2* weighted MRI scans were performed using a 7T scanner. Results demonstrated that cell association/internalization of USPIONs was size- and surface coating-dependent (PEG vs. non-PEG), and higher cellular uptake of 10 and 30 nm non-coated particles was observed in both cell types compared with PEG-coated particles. Cell uptake for 10 and 30 nm non-coated particles was higher in cancer cells from two of three tested donors compared to healthy cells from three donors. There was no significant cytotoxicity observed for all tested particles. Significantly enhanced MRI contrast was observed following exposure to 10 and 30 nm non-coated particles compared to PEG-coated particles in both cell types. In comparison, cancer cells showed more enhanced MRI signals when compared to normal cells. The data indicate that cell responses following exposure to USPIONs are dependent on particle properties. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1032-1042, 2016.
authors.affiliation: Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Sunder S
authors.initials: SS
authors.lastname: Rajan
authors.affiliation: Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Tyner
authors.affiliation: Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Casey
authors.affiliation: Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, 72079.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Dugard
authors.affiliation: Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, 72079.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Jones
authors.affiliation: Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, 72079.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Paredes
authors.affiliation: Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Chekesha S
authors.initials: CS
authors.lastname: Clingman
authors.affiliation: Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, 72079.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Howard
authors.affiliation: Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Goering
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging; D042361:Mammary Glands, Human / Q000000981:diagnostic imaging* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols; C000595209:polyethylene glycol 1000
keywords: breast epithelial cells; contrast agents; iron oxide; magnetic resonance imaging; nanoparticles