Multifunctional dendrimer-entrapped gold nanoparticles for dual mode CT/MR imaging applications Shihui Wen a,1 , Kangan Li b,1 , Hongdong Cai c , Qian Chen c , Mingwu Shen a , Yunpeng Huang a , Chen Peng c , Wenxiu Hou a , Meifang Zhu c , Guixiang Zhang b, ** , Xiangyang Shi a, c, d, * a College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China b Department of Radiology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, PR China c State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, PR China d CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal article info Article history: Received 27 October 2012 Accepted 8 November 2012 Available online 28 November 2012 Keywords: Dendrimers Gold nanoparticles Gadolinium PEGylation CT imaging MR imaging abstract We report the synthesis, characterization, and utilization of gadolium-loaded dendrimer-entrapped gold nanoparticles (GdeAu DENPs) for dual mode computed tomography (CT)/magnetic resonance (MR) imaging applications. In this study, amine-terminated generation five poly(amidoamine) dendrimers (G5.NH 2 ) modified with gadolinium (Gd) chelator and polyethylene glycol (PEG) monomethyl ether were used as templates to synthesize gold nanoparticles (AuNPs). Followed by sequential chelation of Gd(III) and acetylation of the remaining dendrimer terminal amine groups, multifunctional GdeAu DENPs were formed. The formed GdeAu DENPs were characterized via different techniques. We show that the formed GdeAu DENPs are colloidally stable and non-cytotoxic at an Au concentration up to 50 mM. With the coexistence of two radiodense imaging elements of AuNPs and Gd(III) within one NP system, the formed GdeAu DENPs display both r 1 relaxivity for MR imaging mode and X-ray attenuation property for CT imaging mode, which enables CT/MR dual mode imaging of the heart, liver, kidney, and bladder of rat or mouse within a time frame of 45 min. Furthermore, in vivo biodistribution studies reveal that the GdeAu DENPs have an extended blood circulation time and can be cleared from the major organs within 24 h. The strategy to use facile dendrimer technology to design dual mode contrast agents may be extended to prepare multifunctional platforms for targeted multimode molecular imaging of various biological systems. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction The past decade has seen a rapid development in molecular imaging technology, which is able to provide physiological and pathological information with high sensitivity and specificity for disease diagnosis [1e4]. Many imaging modalities such as optical [5,6], computed tomography (CT) [7e9], magnetic resonance (MR) [10e12], position emission tomography (PET) [13,14], and single photon emission computed tomography (SPECT) [15e17] have been and will continue to be used for disease diagnosis. Among these imaging modalities, MR imaging is a powerful, non-invasive imaging technique because of its high spatial resolution and tomographic capabilities [18,19], while CT affords better spatial and density resolution than other imaging modalities [20e22]. For better imaging quality, contrast agents are often required. Conventionally used MR and CT contrast agents are generally based on small molecular agents, which display severe disadvantages such as short half-decay time, renal toxicity at a relatively high concentration, and non-specificity. Recent advances in nanotechnology have shown that various nanoparticulate systems have been used in different biomedical applications, including but not limited to disease diagnosis [23e 25], biological sensing [26e28], drug [29,30] and gene [31e33] delivery. In particular, for MR imaging, Gd(III)- or Mn(II)-based T 1 MR contrast agents [34e36] and magnetic iron oxide nanoparticles (NPs)-based T 2 MR contrast agents [19,37e39] have been widely developed for various MR imaging applications. For CT imaging applications, besides gold NPs (AuNPs) [21,22,40,41], various other * Corresponding author. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China. Tel.: þ86 21 67792656; fax: þ86 21 67792306 804. ** Corresponding author. Tel.: þ86 21 63240090 4166; fax: þ86 21 63240825. E-mail addresses: guixiangzhang@sina.com (G. Zhang), xshi@dhu.edu.cn (X. Shi). 1 Authors contributed equally to this work. Contents lists available at SciVerse ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.biomaterials.2012.11.010 Biomaterials 34 (2013) 1570e1580