DOI: 10.1002/chem.200902344 Heparin-Coated Gold Nanoparticles for Liver-Specific CT Imaging In-Cheol Sun, [a] Dae-Kyung Eun, [b] Jin Hee Na, [a] Seulki Lee, [a] Il-Jin Kim, [c] In-Chan Youn, [a] Chang-Yong Ko, [d] Han-Sung Kim, [d] Dohyung Lim, [e] Kuiwon Choi, [a] Phillip B. Messersmith, [f] Tae Gwan Park, [g] Sang Yoon Kim, [h] Ick Chan Kwon, [a] Kwangmeyung Kim,* [a] and Cheol-Hee Ahn* [b] Since computed tomography (CT) was developed and its resolution, sensitivity, and scan speed rapidly improved, the use of CT in the diagnosis of hepatic disease has been evalu- ated by various investigators. [1] In particular, liver-specific X-ray CT imaging has attracted much attention in cancer di- agnosis and cancer treatment because liver metastases are a common occurrence in the history of a patient affected by various cancers. [2] The liver is the organ most frequently in- volved in metastases due to its high volume of blood flow, the suitable size of sinusoids for trapping metastatic cells, and rich environment for rapid growth. [3] The sensitivity of liver imaging needs to be guaranteed in cancer detection be- cause diagnosis of liver metastasis at an early stage mainly relies on imaging and all liver metastases begin with a mi- croscopic-sized tumor. However, in CT imaging, the detec- tion of liver lesions is impossible without the use of con- trast-enhancing agents, although, even then, the problem of distinguishing between small vessels and small liver tumors is an issue. [4] For this reason, the demand for a tissue-specific X-ray contrast agent has increased, although there are a few products available they have limitations for clinical applica- tion. Although low-molecular-weight iodinated contrast agents are generally used in CT imaging, they have serious limita- tions in clinical applications due to their low liver uptake, rapid renal excretion, and lack of membrane permeation; this leads to renal toxicity and high viscosity of the injecta- ble formulation. [5] To overcome the undesirable pharmacoki- netics and limitations, low-molecular-weight iodinates have been chemically conjugated to high-molecular-weight poly- mers or encapsulated into liposomes and polymeric mi- celles. [6] These macromolecular and nanosized contrast agents display enhanced blood-circulating characteristics in vivo as well as providing liver-specific CT images. However, they still show a lower imaging resolution with respect to differentiating liver tissues from other vessels, organs, and cancers because iodine-based contrast agents inherently pos- sess a lower X-ray absorption coefficient. [7] Another novel inorganic nanoparticle-based CT contrast agent has been proposed. Polymer-coated bismuth sulfide (Bi 2 S 3 ) nanoparti- cles showed high X-ray absorption compared with iodinated imaging agents, [8] but their size and shape were not easy to [a] I.-C. Sun, J.H. Na, Dr. S. Lee, Dr. I.-C. Youn, Dr. K. Choi, Dr. I. C. Kwon, Dr. K. Kim Biomedical Research Center Korea Institute of Science and Technology 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791 (Korea) Fax: (+ 82) 2-958-5909 E-mail: kim@kist.re.kr [b] D.-K. Eun, Dr. C.-H. Ahn Research Institute of Advanced Materials (RIAM) Department of Materials Science and Engineering Seoul National University San 56-1, Sillim, Gwanak, Seoul, 151-744 (Korea) Fax: (+ 82)2-883-8197 E-mail : chahn@snu.ac.kr [c] I.-J. Kim Department of Chemistry, College of Science, Korea University Anam-dong, Seongbuk-gu, Seoul 136-791 (Korea) [d] Dr. C.-Y. Ko, Dr. H.-S. Kim Department of Biomedical Engineering, Yonsei University Wonju, Ganwondo, 220-710 (Korea) [e] Dr. D. Lim Silver Technology Center, Korea Institute of Industrial Technology 35-5 Hongcheon, Ipjang, Cheonan, Chungnam (Korea) [f] Dr. P. B. Messersmith Biomedical Engineering, Northwestern University 2145 Sheridan Road, Evanstron, IL 60208 (USA) [g] Dr. T. G. Park Department of Biological Sciences Korea Advanced Institute of Science Technology Daejeon 305-701 (Korea) [h] Dr. S. Y. Kim Department of Otolaryngology-Head and Neck Surgery Asan Medical Center, College of Medicine, University of Ulsan Seoul 138-736 (South Korea) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200902344. Chem. Eur. J. 2009, 15, 13341 – 13347  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 13341 COMMUNICATION