title: Non-Temperature Induced Effects of Magnetized Iron Oxide Nanoparticles in Alternating Magnetic Field in Cancer Cells.
abstract: This paper reports the damaging effects of magnetic iron-oxide nanoparticles (MNP) on magnetically labeled cancer cells when subjected to oscillating gradients in a strong external magnetic field. Human breast cancer MDA-MB-231 cells were labeled with MNP, placed in the high magnetic field, and subjected to oscillating gradients generated by an imaging gradient system of a 9.4T preclinical MRI system. Changes in cell morphology and a decrease in cell viability were detected in cells treated with oscillating gradients. The cytotoxicity was determined qualitatively and quantitatively by microscopic imaging and cell viability assays. An approximately 26.6% reduction in cell viability was detected in magnetically labeled cells subjected to the combined effect of a static magnetic field and oscillating gradients. No reduction in cell viability was observed in unlabeled cells subjected to gradients, or in MNP-labeled cells in the static magnetic field. As no increase in local temperature was observed, the cell damage was not a result of hyperthermia. Currently, we consider the coherent motion of internalized and aggregated nanoparticles that produce mechanical moments as a potential mechanism of cell destruction. The formation and dynamics of the intracellular aggregates of nanoparticles were visualized by optical and transmission electron microscopy (TEM). The images revealed a rapid formation of elongated MNP aggregates in the cells, which were aligned with the external magnetic field. This strategy provides a new way to eradicate a specific population of MNP-labeled cells, potentially with magnetic resonance imaging guidance using standard MRI equipment, with minimal side effects for the host.
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States of America.
authors.forename: Sudath
authors.initials: S
authors.lastname: Hapuarachchige
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States of America.|Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, United States of America.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States of America.
authors.forename: Ethel J
authors.initials: EJ
authors.lastname: Ngen
authors.affiliation: Cell Biology Imaging Facility, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Smith
authors.affiliation: Cell Biology Imaging Facility, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Delannoy
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, United States of America.|Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, United States of America.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D006801:Humans; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D013696:Temperature; D064726:Triple Negative Breast Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D058185:Magnetite Nanoparticles