Abstract
Recent advances in nanotechnology have contributed to the development of multifunctional nanoparticles as representative nanomedicine. Among different kinds of nanomaterials, iron oxide nanoparticles are among the most promising candidates in combining imaging and therapeutics functions in a single, multimodal platform. This study aimed to develop magnetic nanoparticles to produce heat in the presence of an applied alternating magnetic field, evaluate its therapeutic effects in mouse model and investigate the adjuvant effect for radiotherapy. Gadolinium-doped iron oxide nanoparticles (GdIONPs) were developed for use in tumor therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 with the average magnetic core diameters to be 12nm and 33nm respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38 Wg−1 [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The heating rate for the nanoparticles in vivo and the potential for tumor therapy were determined in a mouse prostate tumor model, transgenic adenocarcinoma of the mouse prostate C1 (TRAMP-C1). The intramuscular TRAMP-C1 tumor treated with doped iron oxide displayed much slower tumor growth. The particle tracking were also demonstrated by MR imaging and laser ablation/inductively coupled plasma (LA-ICP-MS) mapping. The GdIONPs accumulated in tumor region during the treatment could be clearly tracked and quantified by T2-weighted MR imaging and LA-ICP-MS mapping. The therapeutic effects of GdIONP-mediated hyperthermia alone or in combination with radiotherapy were also evaluated. A significant increase in the tumor growth delay was observed following the treatment of thermotherapy only group (2.5 days), radiation therapy only group (4.5 days), and the combined radio-thermotherapy group (10 days). Immunohistochemical staining revealed a reduced hypoxia region with vascular disruption and extensive tumor necrosis following the combined radio-thermotherapy. These results indicate that GdIONP-mediated hyperthermia can improve the efficacy of radiotherapy by its dual functions in high temperature (temperature greater than 45 °C)-mediated thermal ablation and mild-temperature hyperthermia (MTH) (temperature between 39 ~ 42 °C)-mediated reoxygenation.