Crystal-Chemical Design of Hydroxyapatite Magnetic Nanoparticles with Transition Metals

Incorporation of transition metals into hydroxyapatite (HAp) is a way to fabricate biocompatible magnetic nanoparticles (MNPs) for biomedical applications such as cancer hyperthermia and drug delivery. To develop a crystal-chemical design of HAp MNPs, a series of HAps doped with 3d elements (Mn, Fe, Co, Zn, Ni) were synthesized from aqueous solutions and studied using a wide set of methods, including powder X-ray diffraction (PXRD), vibrational spectroscopy, energy-dispersive X-ray (EDX) analysis, electron paramagnetic resonance (EPR), Mössbauer spectroscopy, X-ray photoelectron spectroscopy (XPS), SQUID magnetometry, and magnetic susceptibility measurements. It was shown that the limiting concentrations of all studied transition metals in HAp, and the concentrations beyond which HAp does not crystallize, are directly dependent on the proximity of the ionic radii of the dopants to Ca²⁺ radius: Ca²⁺ > Mn²⁺ > Fe²⁺ > Co²⁺ > Zn²⁺ > Ni²⁺ > Fe³⁺. Doping of HAp with cations containing unpaired electrons in the 3d orbital (Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺) leads to a diamagnetic–paramagnetic transition. The weak ferromagnetic or antiferromagnetic behavior of the synthesis products at cryogenic temperatures most likely originates from 3d-oxide impurities. The magnetic susceptibility of 3d-HAps, which is one of the key parameters of MNPs, is directly dependent not only on the number of unpaired electrons but also on the 3d element content in the HAp lattice. Discovered correlations between magnetic susceptibility and the crystal chemistry of HAp contribute to the development of directed synthesis of HAp MNPs with the required magnetic properties. HAp doped with ∼10 wt % Mn²⁺ with a magnetic susceptibility of ∼4.2 × 10^–5 emu/g, is the most promising candidate for MNPs for biomedical applications.