The characteristics, biodistribution, magnetic resonance imaging and biodegradability of superparamagnetic core–shell nanoparticles Po-Wei Lee a , Sheng-Hsiang Hsu a , Jiun-Jie Wang b , Jin-Sheng Tsai c , Kun-Ju Lin b, d , Shiaw-Pyng Wey b , Fu-Rong Chen e , Chih-Huang Lai f , Tzu-Chen Yen b, d, ** , Hsing-Wen Sung a, * a Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC b Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan, ROC c National Synchrotron Radiation Research Center, Hsinchu, Taiwan, ROC d Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC e Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan, ROC f Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC article info Article history: Received 7 October 2009 Accepted 2 November 2009 Available online 3 December 2009 Keywords: Superparamagnetic iron oxide Glycol chitosan Multifunction Internalization pathway Lysosome abstract An efficient contrast agent for magnetic resonance imaging (MRI) is essential to enhance the detection and characterization of lesions within the body. In this study, we described the development of biode- gradable nanoparticles with a core–shell structure to formulate superparamagnetic iron oxide (CSNP– SPIO) for MRI. The developed nanoparticles were composed of a hydrophobic PLGA core and a positively- charged glycol chitosan shell. The results obtained by transmission electron microscopy, energy dispersive X-ray analysis, electron energy loss spectroscopy, and X-ray diffraction measurement confirmed that the prepared nanoparticles had a core–shell structure with SPIO in their core area. No aggregation of nanoparticles was observed during storage in water, as a result of the electrostatic repulsion between the positively-charged nanoparticles. The magnetic properties of nanoparticles were examined by a vibrating sample magnetometer and a superconducting quantum interference device; the results showed that the superparamagnetism of SPIO was preserved after the CSNP–SPIO formulation. In tracking their cellular internalization pathway, we found that CSNP–SPIO accumulated in lysosomes. In the biodistribution study, a high level of radioactivity was observed in the liver shortly after adminis- tration of the 99m Tc-labeled CSNP–SPIO intravenously. Once taken up by the liver cells, the liver turned dark on T 2 * images. Following cellular internalization, CSNP–SPIO were broken down gradually; there- fore, with time increasing, a significant decrease in the darkness of the liver on T 2 * images was found. The aforementioned results indicate that the developed CSNP–SPIO can serve as an efficient MRI contrast agent and could be degraded after serving their imaging function. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Magnetic resonance imaging (MRI) has become an appealing noninvasive approach in clinical diagnosis; a key to this success has been the development of efficient magnetic contrast agents [1]. The application of magnetic contrast agents in MRI enhances the detection and characterization of lesions within the body [2]. Dextran-based superparamagnetic iron oxide (SPIO) nanoparticles have been extensively used clinically as MRI contrast agents. These dextran-based SPIO nanoparticles are taken up by phagocytic cells and accumulate in the reticuloendothelial system (RES) such as the Kupffer cells of the liver; thus, they are commonly used as a contrast agent for liver MRI [3]. However, SPIO nanoparticles are not strongly associated with dextran and can be readily detached, leading to their aggregation and precipitation under physiological conditions [4]. Additionally, these dextran-based SPIO nano- particles are limited in their capacity of drug loading and the drug dissociates rapidly after administration intravenously [5]. Biodegradable polymers such as poly(D,L-lactic-co-glycolic acid) (PLGA) have been used to encapsulate SPIO in the form of nano- particles [6]. These nanoparticles can be utilized for multifunctional biomedical applications with simultaneous drug-delivery and * Corresponding author. Department of Chemical Engineering/Bioengineering Program, National Tsing Hua University, Hsinchu, Taiwan 30013. Tel.: þ886 3 574 2504; fax: þ886 3 572 6832. ** Corresponding author. Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan, ROC. E-mail addresses: yen1110@adm.cgmh.org.tw (T.-C. Yen), hwsung@che.nthu. edu.tw (H.-W. Sung). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2009.11.010 Biomaterials 31 (2010) 1316–1324