Synthesis of composite magnetic nanoparticles Fe₃O₄ with alendronate for osteoporosis treatment

Abstract

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 (Fe 3 O 4 ) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe 3 O 4 were first synthesized by chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe 3 O 4 particles were then conjugated with Bis to form Bis/Dex/Fe 3 O 4 . Transmission electron microscopy revealed that the average diameter of the Bis/Dex/Fe 3 O 4 particles was ~20 nm. All three kinds of nanoparticles were found to have cubic inverse spinel structure of Fe 3 O 4 by the X-ray diffraction analysis. Fourier transform infrared spectroscopy confirmed that the Dex/Fe 3 O 4 and Bis/Dex/Fe 3 O 4 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/Fe 3 O 4 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/Fe 3 O 4 nanoparticle had the potential for controlling osteoporosis.

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

“…For our knowledge it is a first report showing that IOs can induce apoptosis specifically in osteoclasts while enhanced osteogenic properties of osteoblasts. Similar research has only been performed by Lee et al [51] who fabricated magnetic nanoparticles however with Fe 3 O 4 combined with alendronate for the treatment of osteoporosis. They have found that, fabricated nanoparticles decreased osteoclasts cell survival rate and be applied as a stable MRI contrast agent.…”

“…For our knowledge this is a first report showing that Fe 2 O 3 nanoparticles are able to reduce osteoclasts activity. Research performed by Lee et al [51] revealed that similar to Fe 2 O 3 , Fe 3 O 4 nanoparticles doped with aldosterone, are able to control osteoporosis progression by destroying osteoclasts through thermolysis. Contrary to our results, it was also shown that iron can stimulate osteoclasts differentiation via NF-κB signalling pathway [52] and through increase of RANKL/reactive oxygen species levels [53].…”

Overdenture in terms of preparation and restoration of supporting teeth: Review report

“…Further preservation of supporting teeth and neighbouring alveoli by OD can be provided by inserting of small magnetic cylinders in its base under the remaining teeth. The constant magnetic field is beneficial in reducing the dental plaque index values 7 and food retention around the supporting teeth due to the poor oral hygiene at elders, what confirmed the 12-month study 4 .…”

“…Periodontal tissue that surrounds preserved remaining teeth, intact pulp and alveolar bone below OD may be additional positive biologically stimulated by installation of small magnets and their permanent irradiation 4,16 . The teeth with greater alveolar support and coronal mass should enter the list.…”

“…Overdenture (OD) is applied in removable prosthodontics also for the prevention of the reduction of edentulous alveolar ridge [1][2][3][4][5][6][7] . Magnets insertion into the OD resulted in significant slowing down of periodontal disease 2 and osteoporosis 4,5 as well as antimicrobe effect in the oral cavity 7 . Tooth extraction presents irreversibile mutilation that patients unwillingly agree especially in case of the last remained teeth.…”