A facile aqueous production of bisphosphonated-polyelectrolyte functionalized magnetite nanoparticles for pH-specific targeting of acidic-bone cells

Bone malignancy treatment is being hindered due to the insufficient selectivity of therapeutic nanoparticles towards malignant bone sites. Polyelectrolyte functionalized magnetic nanoparticles having dually specific pH-sensing ability and bisphosphonate moieties, can be an effective solution for selective targeting of bone malignancies. First, polyelectrolyte was prepared via N-carboxycitraconyzation of chitosan (NCCS) followed by successive functionalization with alendronic acid (AL) and fluorescein isothiocyanate (FITC). Then, Fe(3)O(4)-NCCS-FITC-AL nanoparticles were synthesized by a facile one-step microwave-assisted aqueous method via in situ surface functionalization. The formation, crystal structure, and surface conjugation of Fe(3)O(4) nanoparticles with polyelectrolytic stabilizer were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analyses. Synthesized Fe(3)O(4)-NCCS-FITC-AL nanoparticles were superparamagnetic, colloidally stable and highly hemocompatible under physiological conditions. Moreover, at pH 5.0, Fe(3)O(4)-NCCS-FITC-AL nanoparticles formed a precipitate due to inversion of their surface charge. This pH-dependent charge-inversion drastically changed the interactions with erythrocytes and bones. Selective membranolysis of erythrocytes occurred at pH 5.0. The designed nanoparticles showed enough potential for selective targeting of pathological bone sites in early-stage magnetofluorescent imaging and as a therapeutics carrier to treat malignant bone diseases.