Heparin-coated gold nanoparticles for liver-specific CT imaging.

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 evaluated by various investigators. In particular, liver-specific X-ray CT imaging has attracted much attention in cancer diagnosis and cancer treatment because liver metastases are a common occurrence in the history of a patient affected by various cancers. The liver is the organ most frequently involved 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. The sensitivity of liver imaging needs to be guaranteed in cancer detection because diagnosis of liver metastasis at an early stage mainly relies on imaging and all liver metastases begin with a microscopic-sized tumor. However, in CT imaging, the detection of liver lesions is impossible without the use of contrast-enhancing agents, although, even then, the problem of distinguishing between small vessels and small liver tumors is an issue. 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 application. Although low-molecular-weight iodinated contrast agents are generally used in CT imaging, they have serious limitations 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 injectable formulation. To overcome the undesirable pharmacokinetics and limitations, low-molecular-weight iodinates have been chemically conjugated to high-molecular-weight polymers or encapsulated into liposomes and polymeric micelles. 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 possess a lower X-ray absorption coefficient. Another novel inorganic nanoparticle-based CT contrast agent has been proposed. Polymer-coated bismuth sulfide (Bi2S3) nanoparticles showed high X-ray absorption compared with iodinated imaging agents, 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 : [email protected] [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 : [email protected] [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.