Feasibility study of Fe3O4/TaO x nanoparticles as a radiosensitizer for proton therapy

Abstract

We investigated the feasibility of using multifunctional Fe₃O₄/TaO _x (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe₃O₄/TaO _x nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg kg^-1 of 19 nm-diameter Fe₃O₄/TaO _x nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe₃O₄/TaO _x nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150 MeV proton beams irradiated x-ray contrast agent (iodine, BaSO₄), MRI contrast agent (gadolinium, Fe₃O₄), Au, Fe₃O₄/TaO _x (core/shell) nanoparticles and water located at the centre of a 4 × 4 × 4 µm³ water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70 MeV protons irradiated the Au, gadolinium, Fe₃O₄/TaO _x , Fe₃O₄, iodine, and BaSO₄ nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe₃O₄/TaO _x nanoparticles have the potential to be used as a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe₃O₄/TaO _x was half that with Au. However, Fe₃O₄/TaO _x is much cheaper than Au, and it is expected that tumour targeting combined with magnetic field could overcome the low DER.