99mTc-bisphosphonate-coated magnetic nanoparticles as potential theranostic nanoagent.

Novel theranostic nanoplatform is expected to integrate imaging for guiding and monitoring of the tumor therapy with great therapeutic efficacy and fewer side effects. Here we describe the preparation of a multifunctional 99mTc-bisphosphonate-coated magnetic nanoparticles (MNPs) based on Fe3O4 and coated with two hydrophilic bisphosphonate ligands, i.e., methylene diphosphonate (MDP) and 1-hydroxyethane-1,1- diphosphonate (HEDP). The presence of the bisphosphonates on the MNPs surface, enabled their biocompatibility, colloidal stability and successful binding of the radionuclide. The morphology, size, structure, surface charge and magnetic properties of obtained bisphosphonate-coated Fe3O4 MNPs were characterized by transmission electron microscopy, X-ray powder diffraction, dynamic light scattering, laser Doppler electrophoresis, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The specific power absorption values for Fe3O4-MDP and Fe3O4-HEDP were 113 W/g and 141 W/g, respectively, indicated their heating ability under applied magnetic field. Coated MNPs were radiolabeled with 99mTc using stannous chloride as the reducing agent in a reproducible high yield (95% for Fe3O4-MDP and 97% for Fe3O4-HEDP MNPs) and were remained stable in saline and human serum for 24 h. Ex vivo biodistribution studies presented significant liver and spleen uptake in healthy Wistar rats after intravenous administration at all examined time points due to the colloidal nature of both 99mTc-MNPs. Results of scintigraphy studies are in accordance with ex vivo biodistribution studies, demonstrating high in vivo stability of radiolabeled MNPs and therefore results of both methods were proved as accurate information on the biodistribution profile of investigated MNPs. Overall, in vitro and in vivo stability as well as heating ability, indicate that biocompatible radiolabeled bisphosphonate magnetic nanoparticles exhibit promising potential as a theranostic nanoagent.