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.
Highlights
Applications for magnetic nanoparticles (MNP), such as superparamagnetic iron oxide nanoparticles (SPION), in biomedicine are continuously expanding due to their unique properties, which include: biocompatibility and magnetic interaction with external magnetic fields that can generate imaging contrast in magnetic resonance imaging (MRI) [1,2,3], as well as thermal [4] and mechanical effects [5,6]
A unique property of SPION is the efficient generation of heat when exposed to an alternating magnetic field (AMF), which can be used for therapeutic applications [17]
Gradient treated, and MNPlabeled, untreated MDA-MB-231 cells were used as controls for all studies, and no cytotoxicity to the control MDA-MB-231 cells was observed as shown in S1 Appendix
Summary
Applications for magnetic nanoparticles (MNP), such as superparamagnetic iron oxide nanoparticles (SPION), in biomedicine are continuously expanding due to their unique properties, which include: biocompatibility and magnetic interaction with external magnetic fields that can generate imaging contrast in magnetic resonance imaging (MRI) [1,2,3], as well as thermal [4] and mechanical effects [5,6]. A unique property of SPION is the efficient generation of heat when exposed to an alternating magnetic field (AMF), which can be used for therapeutic applications [17]. The effect of AMF on the survivability of cells labeled with MNP without a temperature increase has been reported [25,26,27]
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