The photoluminescence, drug delivery and imaging properties of multifunctional Eu 3þ /Gd 3þ dual-doped hydroxyapatite nanorods Feng Chen a , Peng Huang b , Ying-Jie Zhu a, * , Jin Wu a , Chun-Lei Zhang b , Da-Xiang Cui b, ** a State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China b Department of Bio-Nano Science and Engineering, Research Institute of Micro/Nano Science and Technology, Shanghai JiaoTong University, Shanghai 200240, PR China article info Article history: Received 5 July 2011 Accepted 10 August 2011 Available online 27 August 2011 Keywords: Hydroxyapatite Nanorod Microwave Drug delivery Luminescence Imaging abstract 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 multi- functional Eu 3þ /Gd 3þ dual-doped hydroxyapatite (HAp) nanorods, and the photoluminescence (PL), drug delivery and in vivo imaging of as-prepared Eu 3þ /Gd 3þ doped HAp nanorods. The photoluminescent and magnetic multifunctions of HAp nanorods are realized by the dual-doping with Eu 3þ and Gd 3þ . The PL intensity of doped HAp nanorods can be adjusted by varying Eu 3þ and Gd 3þ concentrations. The magnetization of doped HAp nanorods increases with the concentration of doped Gd 3þ . The as-prepared Eu 3þ /Gd 3þ -doped HAp nanorods exhibit inappreciable toxicity to the cells in vitro. More importantly, the Eu 3þ /Gd 3þ -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 3þ /Gd 3þ -doped HAp nanorods with the photoluminescent function are suitable for in vivo imaging. In vitro and in vivo imaging tests indicate that Eu 3þ /Gd 3þ -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 3þ /Gd 3þ dual-doped HAp nanorods are promising for applications in the biomedical fields such as multifunctional drug delivery systems with imaging guidance. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Hydroxyapatite (HAp) is the most important inorganic constit- uent of biological tissues such as bone and tooth [1,2]. Synthetic HAp is of great value and significance because of its biocompati- bility, and has been investigated for applications in bone repair and tissue engineering, drug and gene delivery, and other biomedical areas [3e7]. HAp with different morphologies such as nanorods, nanotubes, plate-like nanocrystals, nanoparticles and three- dimensional structures were prepared [8e14]. The chemical composition, structure, size, morphology and properties of HAp are usually determined by the preparation process. The facile fast synthesis of HAp with well-defined morphology and desirable properties is very useful and remains a big challenge. The development of multifunctional nanostructured systems holds a promise for the future of clinical treatments to enhance therapeutic efficacy [15e19]. It is highly desirable to develop novel multifunctional nanostructured systems that can achieve simulta- neous in vivo imaging and treatment. Many kinds of nanostructures have been reported for bio-imaging, such as quantum dots [20,21], core/shell silica nanoparticles [22], polymer-coated gold nano- particles [23], carbon nanotubes [24], magnetic nanoparticles [25e28]. HAp nanostructures may serve as the ideal candidate for both bio-imaging and drug delivery. Recently, the research on dual or multifunctional HAp systems for biomedical applications has become a hot topic [29e33]. Lanthanide ions including Eu 3þ and Gd 3þ are functional mimics of Ca 2þ ions and can affect the bone remodeling cycle, and they have potential for the treatment of bone density disorders such as osteoporosis [34,35]. Furthermore, europium ions, with fef intra orbital electronic transitions, lead to the photoluminescence of doped nanoparticles, and can be used for biological imaging [31,36]. On the other hand, gadolinium can be used as a contrast agent to provide brighter magnetic resonance (MR) imaging signal [37]. The application of microwave heating in synthetic chemistry and materials preparation is a fast-growing area of research [38,39]. * Corresponding author. Tel.: þ86 21 52412616; fax: þ86 21 52413122. ** Corresponding author. Fax: þ86 21 34206886. E-mail addresses: y.j.zhu@mail.sic.ac.cn (Y.-J. Zhu), dxcui@sjtu.edu.cn (D.-X. Cui). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2011.08.032 Biomaterials 32 (2011) 9031e9039