Rare-earth (Gd3+,Yb3+/Tm3+, Eu3+) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging

Abstract

Taking advantage of the flexibility of the apatite structure, nano- and micro-particles of hydroxyapatite (HAp) were doped with different combinations of rare earth ions (RE³⁺ = Gd, Eu, Yb, Tm) to achieve a synergy among their magnetic and optical properties and to enable their application in preventive medicine, particularly diagnostics based on multimodal imaging. All powders were synthesized through hydrothermal processing at T ≤ 200 °C. An X-ray powder diffraction analysis showed that all powders crystallized in P6₃/m space group of the hexagonal crystal structure. The refined unit-cell parameters reflected a decrease in the unit cell volume as a result of the partial substitution of Ca²⁺ with smaller RE³⁺ ions at both cation positions. The FTIR analysis additionally suggested that a synergy may exist solely in the triply doped system, where the lattice symmetry and vibration modes become more coherent than in the singly or doubly doped systems. HAp:RE³⁺ optical characterization revealed a change in the energy band gap and the appearance of a weak blue luminescence (λ_ex = 370 nm) due to an increased concentration of defects. The "up"- and the "down"-conversion spectra of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders showed characteristic transitions of Tm³⁺ and Eu³⁺, respectively. Furthermore, in contrast to diamagnetic HAp, all HAp:RE³⁺ powders exhibited paramagnetic behavior. Cell viability tests of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders in human dental pulp stem cell cultures indicated their good biocompatibility.

Figure 1

XRPD and Rietveld refinement of (a) HAp; (b) HAp:Gd; (c) HAp:Gd/Yb/Tm and (d) HAp:Gd/Eu; XRPD pattern (black), Rietveld refined structure (red) and difference curve (blue); Bragg positions are given as bottom bar lines (green). Visualization of structures of HAp and Re³⁺HAp is shown as inset: Gd-violet, Yb- green, Tm- blue, Eu-yellow.

Figure 2

Total FTIR spectra (a) and FTIR spectra focusing on v₃ phosphate stretch in the 950–1150 cm⁻¹ wavenumber range (b) and FTIR spectra focusing on v₄ bend in the 530–630 cm⁻¹ wavenumber range for HAp and for different HAp:RE³⁺ powders (c).

Figure 3

FE-SEM images of (a) HAp; (b) HAp:Gd; (c) HAp:Gd/Yb/Tm; (d) HAp:Gd/Eu and TEM images of (e) HAp:Gd and (f) HAp:Gd/Yb/Tm.

Figure 4

EDS of (a) HAp; (b) HAp:Gd; (c) HAp:Gd/Yb/Tm and (d) HAp:Gd/Eu particles.

Figure 5

Magnetization curves of the HAp:RE³⁺ powders.

Figure 6

The Tauc plots of diffusion reflectance spectra used to measure the Eg of HAp and HAp:RE³⁺ powders.

Figure 7

Photoluminescence emission spectra of (a) pure HAp, HAp:Gd and the HAp:Gd/Yb/Tm powders under 370 nm excitation; photographs of the powders’ blue emission under excitation; (b) HAp:Gd/Eu powder under 394 nm excitation; (c) the time-integrated micro-photoluminescence of the HAp:Gd/Yb/Tm powder under 974 nm excitation and (d) Energy-level diagram of Yb³⁺ and Tm³⁺ transitions following 974 nm excitation.

Figure 8

Time resolved emission spectrum (a) and fluorescence decay curve of the ⁵D₀ → ⁷F₂ emission (b) in HAp:Gd/Eu following excitation at 394 nm.

Figure 9

MTT assay comparing the viability of DPSCs incubated with HAp:Gd/Yb/Tm and HAp:Gd/Eu powders for 24 h (a) and 72 h (b).