Synthesis of composite magnetic nanoparticles Fe₃O₄ with alendronate for osteoporosis treatment

Osteoporosis is a result of imbalance between bone formation by osteoblasts and resorption by osteoclasts (OCs). In the present study, we investigated the potential of limiting the aggravation of osteoporosis by reducing the activity of OCs through thermolysis. The proposed method is to synthesize bisphosphonate (Bis)-conjugated iron (II, III) oxide (Fe₃O₄) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe₃O₄ were first synthesized by chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe₃O₄ particles were then conjugated with Bis to form Bis/Dex/Fe₃O₄. Transmission electron microscopy revealed that the average diameter of the Bis/Dex/Fe₃O₄ particles was ~20 nm. All three kinds of nanoparticles were found to have cubic inverse spinel structure of Fe₃O₄ by the X-ray diffraction analysis. Fourier transform infrared spectroscopy confirmed that the Dex/Fe₃O₄ and Bis/Dex/Fe₃O₄ nanoparticles possessed their respective Dex and Bis functional groups, while a superconducting quantum interference device magnetometer measured the magnetic moment to be 24.5 emu. In addition, the Bis/Dex/Fe₃O₄ nanoparticles were fully dispersed in double-distilled water. Osteoblasts and OCs were individually cultured with the nanoparticles, and an MTT assay revealed that they were non-cytotoxic. An RF system (42 kHz and 450 A) was used to raise the temperature of the nanoparticles for 20 minutes, and the thermal effect was found to be sufficient to destroy OCs. Furthermore, in vivo studies verified that nanoparticles were indeed magnetic resonance imaging contrast agents and that they accumulated after being injected into the body of rats. In conclusion, we developed a water-dispersible magnetic nanoparticle that had RF-induced thermogenic properties, and the results indicated that the Bis/Dex/Fe₃O₄ nanoparticle had the potential for controlling osteoporosis.