Doped Hydroxyapatite Nanorods Research Articles

BMP-2-Loaded HAp:Ln3+ (Ln = Yb, Er, Gd) Nanorods with Dual-Mode Imaging for Efficient MC3t3-E1 Cell Differentiation Regulation.

Effective bone tissue reconstitution improves the treatment success rate of dental implantation and preserves natural teeth during periodontal tissue repair. Hydroxyapatite (HAp) has received much attention in bone remodeling field because its mineralized structure is similar to that of the natural bone tissue. For this reason, it has been used as a carrier for growth factors. Although HAp possesses outstanding biomedical properties, its capacity of loading and releasing bone growth factors and promoting osteogenesis is not well understood. In this study, Ln3+ (Ln = Yb3+, Er3+, Gd3+)-doped HAp (HAp:Ln3+) nanorods were synthesized by one-step hydrothermal method. To improve its biocompatibility and surface properties, bone morphogenetic protein-2 (BMP-2) was loaded onto the surface of HAp:Ln3+ nanorods. The results showed that BMP-2 incorporation promoted bone formation and enhanced the expression of early bone-related gene and protein (RunX2, SP7, OPN). In addition, Yb3+- and Er3+-doped HAp nanorods were examined by upconversion luminescence with 980 nm near-infrared laser irradiation to monitor the delivery position of BMP-2 protein. Furthermore, due to the positive magnetism correlated with the concentration of Gd3+, HAp:Ln3+ with enhanced contrast brightening can be deemed as T1 MIR contrast agents. These findings indicate that HAp doped with rare-earth ions and loaded with BMP-2 has the potential to promote bone tissue repair and execute dual-mode imaging.

Role of citrate in the formation of enamel-like calcium phosphate oriented nanorod arrays

The effect of citrate on the formation of oriented fluoride doped hydroxyapatite nanorods grown on an amorphous calcium phosphate substrate was investigated.

Surface grafting of rare-earth ions doped hydroxyapatite nanorods (HAp:Ln(Eu/Tb)) with hydrophilic copolymers based on ligand exchange reaction: Biological imaging and cancer treatment

Rare-earth ions doped hydroxyapatite nanoparticles (HAp:Ln NPs) have demonstrated to be very promising candidates for biological imaging applications owing to their small size and chemical compositions similar to bone. However, these HAp:Ln NPs with controllable size and morphology should be prepared under hydrothermal treatment with hydrophobic molecules as the protective layers. The hydrophobic nature of these luminescent HAp:Ln NPs largely impeded their applications in biomedical fields. In this study, a novel and effective strategy has been developed for the surface modification of HAp:Ln nanorods through the combination of surface ligand exchange reaction and reversible-addition fragmentation chain transfer (RAFT) polymerization using 2-methacryloyloxyethyl phosphorylcholine (MPC) and itaconic acid (IA) as the monomers. Herein, a small molecule adenosine 5′-monophosphate disodium salt (AMP) that contains a phosphate group and two hydroxyl groups was used to displace the hydrophobic oleic acid on pristine HAp NPs through surface ligand exchange reaction owing to its stronger interaction with HAp NPs. On the other hand, the MPC and IA were introduced on HAp NPs through RAFT polymerization after the chain transfer agent was immobilized on the HAp NPs through the esterification reaction. The poly(IA-MPC) could not only endow the high water dispersibility but also be used for loading anticancer agent cisplatin (CDDP) through coordination interaction. To evaluate their potential biomedical applications, the cell uptake behavior, drug loading capacity and release behavior as well as cell viability of HAp:Ln-AMP-poly(IA-MPC) polymeric composites were examined. We demonstrated that the method developed in this work is very effective for introduction of functional polymers onto HAp:Ln nanorods. The HAp:Ln-AMP-poly(IA-MPC) composites are promising for cell imaging and controlled delivery of CDDP.

A Facile chemical route to synthesize Zn doped hydroxyapatite nanorods for protein drug delivery

Porous and hollow hydroxyapatite (HAp) materials are widely used in the field of protein drug delivery. However, few studies have examined the systematic adsorption and sustained release ability of proteins on the one-dimensional HAp. In this work, undoped HAp and a series of zinc (Zn)-containing hydroxyapatite (ZnHAp) were prepared by a simple hydrothermal process as protein drug carriers. The phase analysis, surface functional groups, morphologies and zeta potentials of the samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and Nano-ZS Zetasizer. The characterization results were found that the crystal structures and chemical functional groups of ZnHAp were similar to those of HAp. And all samples doped with Zn exhibited a uniform rod-like morphology, while the HAp consisted of nanobelts. When the Zn concentration increased, the particle size and lattice parameter of ZnHAp decreased slightly as well as zeta potential. The protein adsorption and release tests indicated that the prepared ZnHAp had a much higher protein payload and the protein-loading amount of 1ZnHAp reached 115.1 mg/g, which was about 3.786 times that of HAp. Moreover, the ZnHAp had a good protein release ability than HAp, using lysozyme (LYS) as the model drug.

Cellular Uptake and Delivery-Dependent Effects of Tb3+-Doped Hydroxyapatite Nanorods.

With the increasing interest in hydroxyapatite (HA) nanostructures for use in biomedicine, the systematic evaluation of their potential effects on biological systems is becoming critically important. In this work, we report the in vitro cellular uptake, in vivo tissue distributions and toxicity of Tb3+-doped HA (HA-Tb) after short-, intermediate-, and long-term exposure. Transmission electron microscopy analysis indicated that HA-Tb was taken up by cells via vesicle endocytosis. Cell proliferation and cytotoxicity assay, combined with confocal laser scanning microscopy, indicated excellent cell viability with no changes in cell morphology at the examined doses. Three HA-Tb delivery methods (intraperitoneal, intragastric, and intravenous) resulted in similar time-dependent tissue distributions, while intraperitoneal injection produced the highest bioavailability. HA-Tb initially accumulated in livers and intestines of rats (4 h to one day after administration), then became increasingly distributed in the kidney and bladder (seven days), and finally decreased in all tissues after 30 to 90 days. No histopathological abnormalities or lesions related to treatment with HA-Tb were observed. These results suggest that HA-Tb has minimal in vitro and in vivo toxicity, regardless of the delivery mode, time, and dose. The findings provide a foundation for the design and development of HA for biological applications.

Large-scale synthesis of water-soluble luminescent hydroxyapatite nanorods for security printing

Luminescent hydroxyapatite nanoparticles, which have excellent biocompatibility, excellent photostability, and strong fluorescence, have received increasing attention as bioprobes in cell imaging. However, they are also excellent candidates for use in ink-jet security printing. Successful products for related applications usually require highly crystalline, mono-dispersible hydroxyapatite nanorods with good colloidal stability and high fluorescence in aqueous media. These requirements are hard to simultaneously satisfy using most synthetic methods. In this paper, we report a simple and versatile hydrothermal method that incorporates the use of sodium citrate to prepare water-dispersible Eu3+-doped hydroxyapatite nanorods. The hydroxyapatite nanorods obtained using this method are highly crystalline rod-shaped particles with an average length of 50–80nm and an average diameter of 15–30nm. Dispersions of these hydroxyapatite nanorods, which are transparent with a slightly milky color under natural light and a bright red color when excited with 241nm UV light, display zeta potentials of −35mV and hydrodynamic diameters of 120nm. These dispersions remain colloidally stable for a few months. Dispersions with these properties could be easily applied to security printing for confidential information storage and anti-counterfeiting technologies.

The photoluminescence, drug delivery and imaging properties of multifunctional Eu 3+/Gd 3+ dual-doped hydroxyapatite nanorods

The design and synthesis of multifunctional systems with high biocompatibility are very significant for the future of clinical applications. Herein, we report a microwave-assisted rapid synthesis of multifunctional Eu 3+/Gd 3+ dual-doped hydroxyapatite (HAp) nanorods, and the photoluminescence (PL), drug delivery and in vivo imaging of as-prepared Eu 3+/Gd 3+ doped HAp nanorods. The photoluminescent and magnetic multifunctions of HAp nanorods are realized by the dual-doping with Eu 3+ and Gd 3+. The PL intensity of doped HAp nanorods can be adjusted by varying Eu 3+ and Gd 3+ concentrations. The magnetization of doped HAp nanorods increases with the concentration of doped Gd 3+. The as-prepared Eu 3+/Gd 3+-doped HAp nanorods exhibit inappreciable toxicity to the cells in vitro. More importantly, the Eu 3+/Gd 3+-doped HAp nanorods show a high drug adsorption capacity and sustained drug release using ibuprofen as a model drug, and the drug release is governed by a diffusion process. Furthermore, the noninvasive visualization of nude mice with subcutaneous injection indicates that the Eu 3+/Gd 3+-doped HAp nanorods with the photoluminescent function are suitable for in vivo imaging. In vitro and in vivo imaging tests indicate that Eu 3+/Gd 3+-doped HAp nanorods have a potential in applications such as a multiple-model imaging agent for magnetic resonance (MR) imaging, photoluminescence imaging and computed tomography (CT) imaging. The Eu 3+/Gd 3+ dual-doped HAp nanorods are promising for applications in the biomedical fields such as multifunctional drug delivery systems with imaging guidance.

Synthesis of fluorescent core–shell hydroxyapatite nanoparticles

Lanthanide-doped fluorescent hydroxyapatite/silica core–shell nanorods, 50–100 nm in length and 30 nm in width, were prepared by precipitation of calcium phosphate in the presence of Eu3+ and Y3+ ions at 60 °C, followed by hydrothermally enhanced crystallization, stabilization with poly(ethyleneimine), and reaction with tetraethyl orthosilicate. The fluorescence intensity of the Eu3+-doped hydroxyapatite nanorods was enhanced threefold by co-doping with Y3+ and doubled after hydrothermal treatment. Significantly, fluorescence quenching by water was reduced in the presence of the thin silica nanoshell to give a further doubling of the fluorescence intensity compared with lanthanide-doped hydroxyapatite nanoparticles prepared in the absence of tetraethyl orthosilicate. Our results suggest that a combination of lanthanide doping, controlled crystallization and core–shell fabrication is a promising route to the preparation of biocompatible calcium phosphate nanoparticles with enhanced fluorescence for potential use in biomedical applications.