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

Marija Mirković; Magdalena Radović; Dragana Stanković; Zorana Milanović; Drina Janković; Milovan Matović; Marija Jeremić; Bratislav Antić; Sanja Vranješ-Đurić

doi:10.1016/j.msec.2019.04.034

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

Mater Sci Eng C Mater Biol Appl. 2019 Sep:102:124-133. doi: 10.1016/j.msec.2019.04.034. Epub 2019 Apr 13.

Authors

Marija Mirković¹, Magdalena Radović², Dragana Stanković², Zorana Milanović², Drina Janković², Milovan Matović³, Marija Jeremić³, Bratislav Antić⁴, Sanja Vranješ-Đurić²

Affiliations

¹ Laboratory for Radioisotopes, Vinča Institute of Nuclear Sciences, University of Belgrade, P. O. Box 522, 11001 Belgrade, Serbia. Electronic address: mmarija@vin.bg.ac.rs.
² Laboratory for Radioisotopes, Vinča Institute of Nuclear Sciences, University of Belgrade, P. O. Box 522, 11001 Belgrade, Serbia.
³ Centre of Nuclear Medicine, Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia.
⁴ Laboratory of Theoretical and Condensed Matter Physics, Vinča Institute of Nuclear Sciences, University of Belgrade, P. O. Box 522, 11001 Belgrade, Serbia.

PMID: 31146983
DOI: 10.1016/j.msec.2019.04.034

Abstract

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.

Keywords: Bisphosphonates; Magnetic nanoparticles; Radiolabeling; Scintigraphy; Theranostic agent.

MeSH terms

Animals
Coated Materials, Biocompatible / chemistry*
Diphosphonates / chemistry*
Hyperthermia, Induced
Magnetite Nanoparticles / chemistry*
Magnetite Nanoparticles / ultrastructure
Male
Organotechnetium Compounds / chemistry*
Particle Size
Rats, Wistar
Temperature
Theranostic Nanomedicine*
Time Factors
Tissue Distribution
X-Ray Diffraction

Substances

Coated Materials, Biocompatible
Diphosphonates
Magnetite Nanoparticles
Organotechnetium Compounds
technetium 99m methylene bisphosphonate