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

Abstract

Functionalization of highly pure rutile phase titanium dioxide (TiO2) 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 TiO2 by ultraviolet irradiation. The reaction time was varied to control the crystal growth of the BPCC around the TiO2 core, resulting in a functionalized material with different shell thicknesses: TiO2-core:nano-Ca@ZOLE-shell-† (5 min) and TiO2-core:nano-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 TiO2 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 TiO2-core:nano-Ca@ZOLE-shell-† was determined through thermogravimetric analysis, estimating a ratio of ∼1:3 (TiO2:BPCC). The cytotoxicity of TiO2-core:nano-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 TiO2-core:nano-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 TiO2 for the development of a novel functionalized material with the potential to treat and prevent osteolytic metastases.

Design of Extended Bisphosphonate-Based Coordination Polymers as Bone-Targeted Drug Delivery Systems for Breast Cancer-Induced Osteolytic Metastasis and Other Bone Therapies

“…Specifically, BBPA-Ca form II possesses the largest channels (8 × 12 Å 2 ) and the capacity to preserve its structure in neutral environments and degrade drastically in acidic media. The PIT-nano-emulsion method has been previously employed to decrease the particle size of various crystalline materials, including BPCCs. − This method was adapted within this work to reduce the particle size of BBPA-Ca form II (Supporting Information). First, the PIT of an emulsion composed of BBPA in heptane and Brij L4 was determined.…”

“…The phase inversion temperature (PIT) nano-emulsion method has been employed to decrease the particle size of crystalline materials, including BPCCs. − T he synthesis of BBPA-Ca form II was adapted using this method (Supporting Information) and yielded an isostructural material, nano-Ca@BBPA. The particle size distribution and polydispersity of nano-Ca@BBPA in 10% FBS/PBS were assessed after 0, 24, and 48 h by DLS.…”

Immobilization of Alendronate on Zirconium Phosphate Nanoplatelets

“…The effective immobilization of bioactive species on solid substrates without changing their original structure and bioactivity, which allows for maintaining drug release over a sustained period, has attracted increasing interest among researchers along with rapid advances in biodevices [ 9 , 10 ]. The topotactic exchange method can be considered an alternative to the preparation, via the intercalation reaction, of drug delivery systems based on ZP compounds.…”