title: Accumulation and biological effects of cobalt ferrite nanoparticles in human pancreatic and ovarian cancer cells.
abstract: OBJECTIVE
  Superparamagnetic iron oxide nanoparticles (SPIONs) emerge as a promising tool for early cancer diagnostics and targeted therapy. However, both toxicity and biological activity of SPIONs should be evaluated in detail. The aim of this study was to synthesize superparamagnetic cobalt ferrite nanoparticles (Co-SPIONs), and to investigate their uptake, toxicity and effects on cancer stem-like properties in human pancreatic cancer cell line MiaPaCa2 and human ovarian cancer cell line A2780.
  
  
  METHODS
  Co-SPIONs were produced by Massart's co-precipitation method. The cells were treated with Co-SPIONs at three different concentrations (0.095, 0.48, and 0.95μg/mL) for 24 and 48h. Cell viability and proliferation were analyzed after treatment. The stem-like properties of cells were assessed by investigating the cell clonogenicity and expression of cancer stem cell-associated markers, including CD24/ESA in A2780 cell line and CD44/ALDH1 in MiaPaCa2 cell line. Magnetically activated cell sorting was used for the separation of magnetically labeled and unlabeled cells.
  
  
  RESULTS
  Both cancer cell lines accumulated Co-SPIONs, however differences in response to nanoparticles were observed between MiaPaCa2 and A2780 cell. In particular, A2780 cells were more sensitive to exposition to Co-SPIONs than MiaPaCa2 cells, indicating that a safe concentration of nanoparticles must be estimated individually for a particular cell type. Higher doses of Co-SPIONs decreased both the clonogenicity and ESA marker expression in A2780 cells.
  
  
  CONCLUSIONS
  Co-SPIONs are not cytotoxic to cancer cells, at least when used at a concentration of up to 0.95μg/mL. Co-SPIONs have a dose-dependent effect on the clonogenic potential and ESA marker expression in A2780 cells. Magnetic detection of low concentrations of Co-SPIONS in cancer cells is a promising tool for further applications of these nanoparticles in cancer diagnosis and treatment; however, extensive research in this field is needed.
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania. Electronic address: vita.pasukoniene@nvi.lt.
authors.forename: Vita
authors.initials: V
authors.lastname: Pašukonienė
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Agata
authors.initials: A
authors.lastname: Mlynska
authors.affiliation: Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Simona
authors.initials: S
authors.lastname: Steponkienė
authors.affiliation: Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Vilius
authors.initials: V
authors.lastname: Poderys
authors.affiliation: Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; Biophotonics Group of Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania.
authors.forename: Marija
authors.initials: M
authors.lastname: Matulionytė
authors.affiliation: Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Vitalijus
authors.initials: V
authors.lastname: Karabanovas
authors.affiliation: Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Urtė
authors.initials: U
authors.lastname: Statkutė
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Rasa
authors.initials: R
authors.lastname: Purvinienė
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Jan Aleksander
authors.initials: JA
authors.lastname: Kraśko
authors.affiliation: Laboratory of Nanostructures, State Research Institute Centre for Physical Sciences and Technology, Vilnius, Lithuania.
authors.forename: Arūnas
authors.initials: A
authors.lastname: Jagminas
authors.affiliation: Laboratory of Nanostructures, State Research Institute Centre for Physical Sciences and Technology, Vilnius, Lithuania.
authors.forename: Marija
authors.initials: M
authors.lastname: Kurtinaitienė
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Marius
authors.initials: M
authors.lastname: Strioga
authors.affiliation: Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; Biophotonics Group of Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania.
authors.forename: Ričardas
authors.initials: R
authors.lastname: Rotomskis
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005290:Ferric Compounds / Q000378:metabolism* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D053758:Nanoparticles / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010316:Particle Size
chemical_list: D005290:Ferric Compounds; C569492:cobalt ferrite; D003035:Cobalt
keywords: Cancer stem-like cells; Cytotoxicity; Ovarian cancer; Pancreatic cancer; Superparamagnetic cobalt ferrite nanoparticles