Preparation and characterization of MRI-active gadolinium nanocomposite particles for neutron capture therapy† Heui Kyoung Cho, a Hyun-Jong Cho, b Saifullah Lone, a Dae-Duk Kim, b Jeong Hyun Yeum c and In Woo Cheong * a Received 15th April 2011, Accepted 21st July 2011 DOI: 10.1039/c1jm11608h We demonstrate the synthesis and characteristics of MRI-active Gd 2 O 3 core/SiO 2 shell/poly(2- methacryloyloxyethyl phosphorylcholine) corona composite nanoparticles (Gd 2 O 3 @SiO 2 @PMPC NPs). The prepared NPs have a number of attractive features in cancer diagnosis and neutron capture therapy (NCT): biocompatibility, colloidal stability, low cytotoxicity, nucleus affinity, passive targeting, etc. Monodisperse and highly crystalline Gd 2 O 3 NPs were prepared using a polyol protocol to control the average particle size and surface properties. The Gd 2 O 3 NPs were then functionalized with SiO 2 and a biomimetic layer of PMPC, to achieve reduced toxicity and enhanced nucleus affinity, for use as an MRI-active Gd-NCT agent. The size of the NPs was tailored to be from 50 to 100 nm for passive accumulation in tumor tissue through loosened capillary vessels. The morphologies and structures of Gd 2 O 3 , Gd 2 O 3 @SiO 2 –Br, and Gd 2 O 3 @SiO 2 @PMPC NPs were studied by FT-IR, XRD, HR-TEM, and TGA. In vitro cytotoxicity was investigated with three kinds of normal and cancer cells, and in vitro and in vivo MRI analyses were performed to confirm the contrast ability, accumulation, and sustentation of NPs in tumor tissues. 1. Introduction Gadolinium (Gd), because of its high paramagnetic properties and strong relaxation effects, arising from its seven unpaired electrons in the 4f shell, has attracted much attention in biomedical applications. It has been developed as an MRI contrast agent for positive intensity images and has also been investigated as a therapeutic agent for neutron capture therapy (NCT) since the late 1980s. 1,2 NCT is a promising cancer thera- peutic approach because it can effectively eliminate cancer cells using a low-energy neutron beam. To kill tumor cells, Gd-NCT uses emitted photons and electrons, especially Auger electrons, resulting from thermal neutron capture reactions of gadolinium- 157 ( 157 Gd). Earlier NCT studies focused on boron-10 ( 10 B); however, Gd-NCT was considered to have advantages over B-NCT because its thermal neutron capture cross-section is 66 times higher, and thus it requires shorter neutron irradiation times. 3 For these reasons, Gd has been intensively studied as a Gd-NCT agent, especially gadolinium chelates, e.g., gadoli- nium tetraazacyclododecanetetraacetic acid (Gd-DOTA) and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), to reduce the strong toxicity of Gd(III) ions. 4–6 However, these Gd (III) chelates exhibit rapid excretion because of their low molec- ular weights and poor selectivity in tumor tissues. These obsta- cles have limited the success of Gd(III) chelates in both MRI and NCT applications. To overcome these drawbacks, several methods for encapsulating Gd(III) chelates have been developed. 7–9 There are considerable similarities between the design criteria for MRI and Gd-NCT, such as biocompatibility, shelf-life stability, effective delivery, and sufficient accumulation of Gd in tumor sites. Moreover, one of the key factors for Gd-NCT is effective biodistribution of the Gd agent in close proximity to the DNA in a cancer cell because the emitted Auger electrons display high ionization over a short range of several tens of nano- metres. 10 To achieve these goals, 2-methacryloyloxy- ethylphosphorylcholine (MPC) was selected to endow Gd-NCT agents with nucleus affinity as well as biocompatibility. It has been proved that MPC reduces biofouling, such as protein adsorption and adhesion of bacteria, in biomembrane structures because of its biomimetic features. 11,12 Stasio et al. investigated the localization of physiological elements such as phosphorus, calcium, carbon, potassium, and sodium in cell nuclei. 13 Among these elements, phosphorus showed the highest concentration in a Department of Applied Chemistry, Kyungpook National University, 1370 Sankyuk-3-dong, Buk-gu, Daegu, 702-701, South Korea. E-mail: inwoo@ knu.ac.kr; Fax: +82 53 950 6594; Tel: +82 53 950 7590 b College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-742, South Korea c Department of Advanced Organic Materials Science and Engineering, Kyungpook National University, 1370 Sankyuk-3-dong, Buk-gu, Daegu, 702-701, South Korea † Electronic supplementary information (ESI) available. See DOI: 10.1039/c1jm11608h 15486 | J. Mater. Chem., 2011, 21, 15486–15493 This journal is ª The Royal Society of Chemistry 2011 Dynamic Article Links C < Journal of Materials Chemistry Cite this: J. Mater. Chem., 2011, 21, 15486 www.rsc.org/materials PAPER Published on 24 August 2011. Downloaded by King Abdullah Univ of Science and Technology on 20/11/2014 18:49:17. View Article Online / Journal Homepage / Table of Contents for this issue