Single-phased luminescent mesoporous nanoparticles for simultaneous cell imaging and anticancer drug delivery Weihua Di a, b, c, * , Xinguang Ren d , Haifeng Zhao d , Naoto Shirahata c, e , Yoshio Sakka b, c, ** , Weiping Qin a, *** a State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, PR China b World Premier International Research (WPI) Center Initiative on Materials Nanoarchitronics (MANA), National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan c Advanced Ceramics Group, Advanced Materials Processing Unit, NIMS, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan d Key Laboratory of Excited-state Processes, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 3888 Eastern South Lake Road, Changchun 130033, PR China e PRESTO, Japan Science and Technology Agency (JST) 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan article info Article history: Received 25 May 2011 Accepted 9 June 2011 Available online 13 July 2011 Keywords: Lanthanide oxides Mesopore Luminescence Cell imaging Drug delivery Cytotoxicity abstract Multifunctional materials for biological use have mostly been designed with composite or hybrid nanostructures in which two or more components are incorporated. The present work reports on a multifunctional biomaterial based on single-phased luminescent mesoporous lanthanide oxide nanoparticles that combine simultaneous drug delivery and cell imaging. A simple strategy based on solid-state-chemistry thermal decomposition process was employed to fabricate the spherical meso- porous Gd 2 O 3 :Eu nanoparticles with homogeneous size distribution. The porous nanoparticles devel- oped by this strategy possess well-defined mesopores, large pore size and volume, and high specific surface area. The mesoporous features of nanoparticles impart the material with capabilities of loading and releasing the drug with a relatively high loading efficiency and a sustained release behavior of drugs. The DOX-loaded porous Gd 2 O 3 nanoparticles are able to kill the cancer cells efficiently upon incubation with the human cervical carcinoma (HeLa) cells, indicating the potential for treatment of cancer cells. Meanwhile, the intrinsic luminescence of Gd 2 O 3 :Eu nanoparticles gives the function of optical imaging. Therefore, the drug release activity and effect of drugs on the cells can be effectively monitored via luminescence of nanoparticles themselves, realizing multifunctionality of simultaneous cell imaging and anticancer drug delivery in a single-phased nanoparticle. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Many drugs, especially cancer-therapy drugs, have severe side effect that is caused by the nonspecific uptake of anticancer drugs by healthy tissues/organs such as kidney, liver, bone marrow and heart. Encapsulation of such drugs in carriers could reduce these side effects significantly, because a carrier can protect organs from a toxic drug and prevent the decomposition/denaturing of the drugs prior to reaching the targeted cells [1,2]. Moreover, encap- sulation enables drugs to be released in a controlled way [1e3]. Mesoporous materials have been shown as a potentially useful drug carrier because of their unique characteristics such as high surface area, tunable pore size and volume, and well-defined surface properties for modifications [3e5]. To achieve multifunc- tional purpose of biological use of porous materials, extensive efforts have been devoted to designing a composite or hybrid nanostructure in which two or more components are incorporated to give the final material multifunctional capabilities. Therefore, the fabrication of the heterostructured mesoporous particles has attracted considerable attention in recent years, since they can combine the drug delivery with other biological functions, such as fluorescence imaging and magnetic resonance (MR) imaging or both into a composite/hybrid nanostructure, thus simultaneously fulfilling multifunctionalities [2,6e12]. A thin layer of mesoporous silica is coated onto the NaYF 4 up-conversion nanocrystals to form core-shell NaYF 4 @silica nanoparticles for synergistic imaging and * Corresponding author. State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, PR China. ** Corresponding author. World Premier International Research (WPI) Center Initiative on Materials Nanoarchitronics (MANA), National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan *** Corresponding author. E-mail addresses: weihdi@yahoo.com.cn (W. Di), SAKKA.Yoshio@nims.go.jp (Y. Sakka), wpqin@jlu.edu.cn (W. Qin). 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.2011.06.019 Biomaterials 32 (2011) 7226e7233