Functionalization of Titanium Dioxide by Surface Crystallization of Bisphosphonate-Based Coordination Complexes.

Functionalization of highly pure rutile phase titanium dioxide (TiO) particles with a selected bisphosphonate-based coordination complex (BPCC), ZOLE-Ca form II, was achieved through in situ surface crystallization. The hydrothermal reaction of the selected BPCC was carried out in the presence of photoactivated rutile phase TiO by ultraviolet irradiation. The reaction time was varied to control the crystal growth of the BPCC around the TiO core, resulting in a functionalized material with different shell thicknesses: TiO-core:ZOLE-shell-† (5 min) and TiO-core:Ca@ZOLE-shell-‡ (10 min). The crystal phase assessment of the BPCC and the polymorphic phase purity of the metal oxide were determined after immobilization through Raman spectroscopy and powder X-ray diffraction. The results initially suggested that the crystallization of a shell comprising the selected BPCC surrounding a highly pure rutile phase TiO core was achieved through controlled in situ surface crystallization. Morphological changes, elemental composition and exact atomic distribution in the functionalized materials were addressed employing scanning electron microscopy coupled with energy-dispersive spectroscopy. These analyses unambiguously confirmed that after 5 min, successful incorporation of a thin BPCC shell on the surface of the metal oxide particles was achieved. Particle size distribution measurements revealed an average particle size of 495 d.nm for the functionalized material after the immobilization process. Quantitative determination of the BPCC shell content in TiO-core:Ca@ZOLE-shell-† was determined through thermogravimetric analysis, estimating a ratio of ∼1:3 (TiO:BPCC). The cytotoxicity of TiO-core:Ca@ZOLE-shell-† against MDA-MB-231 (cancer cell model) and hFOB 1.19 (normal osteoblast-like cell model) cell lines was investigated. The results demonstrated significant cell growth inhibition for TiO-core:Ca@ZOLE-shell-† against MDA-MB-231, specifically at a concentration of 7.5 μM (% RCL = 46 ± 2%, 72 h). Under the same conditions, the functionalized material did not present cytotoxicity against hFOB 1.19 (% RCL ∼ 100%). These important outcomes provide evidence of the surface crystallization of BPCCs onto rutile phase TiO for the development of a novel functionalized material with the potential to treat and prevent osteolytic metastases.