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Published on: May 22, 2020
Micron-sized iron oxide particles for both MRI cell tracking and magnetic fluid hyperthermia treatment
Laurence Dallet1, Dimitri Stanicki2, Pierre Voisin1
1Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536, CNRS/Univ. Bordeaux, 146 rue Léo Saignat, 33076, Bordeaux, France.
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.
Insights
Micrometric iron oxide particles (IOP) show potential for cancer therapy. One type, ScreenMAG, effectively heats under an alternating magnetic field, leading to glioma cell death and reduced tumor volume in mice treated with Magnetic Fluid Hyperthermia (MFH).
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Micrometric iron oxide particles (IOP) are utilized in cellular Magnetic Resonance Imaging (MRI) and Magnetic Fluid Hyperthermia (MFH).
- Understanding IOP internalization and heat generation is crucial for optimizing MFH cancer treatments.
- Micrometric IOP offer high detection sensitivity, but their biological interactions require further investigation.
Purpose of the Study:
- To characterize micrometric IOP and analyze their endocytic pathways in glioma cells.
- To evaluate the Specific Absorption Rate (SAR) and cytotoxicity of IOP under an Alternating Magnetic Field (AMF).
- To assess the efficacy of MFH treatment using IOP in a preclinical glioma model.
Main Methods:
- Transmission Electron Microscopy (TEM) for IOP characterization.
- Endocytic pathway analysis in glioma cells.
- AMF induction for SAR and cytotoxicity assessment.
- In vivo T2-weighted imaging to monitor tumor growth in mice.
Main Results:
- Two commercial micrometric IOP exhibited similar structures and relaxivities but distinct endocytic pathways.
- ScreenMAG particles demonstrated significant heating (SAR = 113 W g⁻¹ Fe) under AMF.
- 60% of ScreenMAG-labeled glioma cells underwent apoptosis after 1 hour of AMF exposure.
- MFH treatment with ScreenMAG resulted in an 89% response rate, with reduced tumor volume in mice.
Conclusions:
- Micrometric IOP internalization varies depending on particle type.
- ScreenMAG particles are effective for MFH, inducing significant cell death and tumor regression.
- This study demonstrates the comprehensive investigation of micrometric IOP from characterization to in vivo cancer treatment application.
