Thermotherapy for Na+/I- symporter-expressing cancer using anti-Na+/I- symporter antibody-conjugated magnetite nanoparticles

Abstract

Surgery, followed by remnant ablation with radioactive iodine (I-131), is used for treating differentiated thyroid carcinoma (DTC) as the sodium？iodine (Na-I) symporter (NIS) is highly expressed in the thyroid and DTC cells. Our aim was to investigate the feasibility of using anti-NIS antibody-conjugated magnetite nanoparticles (NIS-MNPs) as a diagnostic and therapeutic agent for DTC by studying NIS-MNP in an NIS over-expressing HeLa (HeLa-NIS) cell line and a subcutaneous HeLa-NIS tumor-bearing mouse model. Immunofluorescence was used to determine if NIS-MNP could bind to HeLa-NIS, and its therapeutic effect was investigated using HeLa-NIS cells after alternating magnetic field (AMF) irradiation. Magnetic resonance imaging (MRI) was performed to visualize the normal thyroid gland of nude mice after intravenous injection of NIS-MNP. NIS-MNPs were injected into the cancer nodules of the mouse model, which were irradiated under AMF for 1 h twice at 24-h intervals. Accumulation of NIS-MNP was examined using MRI and tumor volume was measured over seven days. Results showed that NIS-MNP bound effectively to the surface of HeLa-NIS cells, and AMF inhibited growth of NIS-MNP-treated HeLa-NIS cells. Normal thyroid glands of mice were enhanced by NIS-MNP treatment in T2-weighted MRI. Inhibition of tumor growth was observed after AMF irradiation in the NIS-MNP group. In conclusion, NIS-MNP is a feasible diagnostic and therapeutic tool for localizing and treating NIS-expressing tumors such as DTC when coupled with AMF irradiation