Abstract
Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r2 relaxivities (100 mM−1 s−1) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g−1 Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.
Highlights
Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF)
ScreenMAG and MPIO particles are of irregular shapes
7 days after the AMF application, IOP were mainly detected within the cells. This present research studied the complete process of micrometric particles—from particle characterization to intracellular internalization pathway and in vivo application—to evaluate if a micrometric-sized particle is valuable for MFH treatments
Summary
Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Their larger surface enables more moieties (like antibodies, aptamers, etc.) to be grafted per particle[1] in order to increase targeting efficiency[2] Due their large size and the high iron content per particle, single particles can be detected by T2*-weighted MRI3, which is essential for cell tracking over long periods of time. Micrometric IOP from Bangs Laboratories have been used for cancer cell tracking[4,10] These commercial IOP have interesting properties, including an efficient internalization, biocompatibility, long stability within cells and, a high sensitivity of detection by MRI. We hypothesized that due to the high amount of iron per particle, large IOP can be beneficial for MFH treatment
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