title: Increased cellular uptake of biocompatible superparamagnetic iron oxide nanoparticles into malignant cells by an external magnetic field.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are used as delivery systems for different therapeutics including nucleic acids for magnetofection-mediated gene therapy. The aim of our study was to evaluate physicochemical properties, biocompatibility, cellular uptake and trafficking pathways of the custom-synthesized SPIONs for their potential use in magnetofection. Custom-synthesized SPIONs were tested for size, shape, crystalline composition and magnetic behavior using a transmission electron microscope, X-ray diffractometer and magnetometer. SPIONs were dispersed in different aqueous media to obtain ferrofluids, which were tested for pH and stability using a pH meter and zetameter. Cytotoxicity was determined using the MTS and clonogenic assays. Cellular uptake and trafficking pathways were qualitatively evaluated by transmission electron microscopy and quantitatively by inductively coupled plasma atomic emission spectrometry. SPIONs were composed of an iron oxide core with a diameter of 8-9 nm, coated with a 2-nm-thick layer of silica. SPIONs, dispersed in 0.9% NaCl solution, resulted in a stable ferrofluid at physiological pH for several months. SPIONs were not cytotoxic in a broad range of concentrations and were readily internalized into different cells by endocytosis. Exposure to neodymium-iron-boron magnets significantly increased the cellular uptake of SPIONs, predominantly into malignant cells. The prepared SPIONs displayed adequate physicochemical and biomedical properties for potential use in magnetofection. Their cellular uptake was dependent on the cell type, and their accumulation within the cells was dependent on the duration of exposure to an external magnetic field.
authors.affiliation: Kolektor Group, Nanotesla Institute, Stegne 29, 1521, Ljubljana, Slovenia. sara.prijic@nanotesla.si
authors.forename: Sara
authors.initials: S
authors.lastname: Prijic
authors.forename: Janez
authors.initials: J
authors.lastname: Scancar
authors.forename: Rok
authors.initials: R
authors.lastname: Romih
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Bregar
authors.forename: Andrej
authors.initials: A
authors.lastname: Znidarsic
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055909:Magnetic Field Therapy / Q000379:methods*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009369:Neoplasms / Q000628:therapy*; D010316:Particle Size
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide