Magneto-mechanical effects of magnetite nanoparticles on Walker-256 carcinosarcoma heterogeneity, redox state and growth modulated by an inhomogeneous stationary magnetic field

Abstract

Iron oxide (Fe3O4) magnetic nanoparticles (MNs) delivered to the tumor under the influence of magnetic fields can generate reactive oxygen species (ROS) that affect the activity of mitochondrial enzymes, DNA damage and abnormal cell growth. Previous investigations used rotating magnetic fields to inhibit tumor growth. Herein, we question whether the magneto-mechanical effects of MNs under an inhomogeneous stationary magnetic field (ISMF) can modulate tumor heterogeneity, ROS and growth. Animals with Walker-256 carcinosarcoma in group 1 underwent no treatment (control), group 2 received MNs, while group 3 was treated with MNs + ISMF. MNs were injected with tumor cells. ISMF treatment was given every other day starting 2 days after implantation. MNs + ISMF showed a 51% increase in the tumor growth factor compared with MNs alone. Elevated levels of free iron and superoxide radical as well as decreased lactoferrin and NO-FeS-proteins were measured after MNs + ISMF treatment. The present study provides experimental evidence that the magnetic force exerted by ISMF upon MNs initiates morphological heterogeneity, modulates ROS generation and promotes tumor growth. Therefore, these findings propose to circumvent the negative effects of MNs by a shortened duration of targeted delivery, application of slowly changing ISMFs, and combination of ISMFs with alternating magnetic fields to modulate iron-dependent redox reactions.