Simple and Generalized Synthesis of Oxide-Metal Heterostructured Nanoparticles and their Applications in Multimodal Biomedical Probes Sang-Hyun Choi, † Hyon Bin Na, † Yong Il Park, † Kwangjin An, † Soon Gu Kwon, † Youngjin Jang, † Mi-hyun Park, † Jaewon Moon, † Jae Sung Son, † In Chan Song, ‡ Woo Kyung Moon, ‡ and Taeghwan Hyeon* ,† National CreatiVe Research InitiatiVe Center for Oxide Nanocrystalline Materials and School of Chemical and Biological Engineering, Seoul National UniVersity, Seoul 151-744, Korea, and Department of Radiology, Seoul National UniVersity College of Medicine, Seoul National UniVersity Hospital, Seoul 110-744, Korea Received July 9, 2008; E-mail: thyeon@snu.ac.kr Abstract: Heterostructured nanoparticles composed of metals and Fe 3 O 4 or MnO were synthesized by thermal decomposition of mixtures of metal -oleate complexes (for the oxide component) and metal -oleylamine complexes (for the metal component). The products included flowerlike-shaped nanoparticles of Pt-Fe 3 O 4 and Ni-Fe 3 O 4 and snowmanlike-shaped nanoparticles of Ag-MnO and Au-MnO. Powder X-ray diffraction patterns showed that these nanoparticles were composed of face-centered cubic (fcc)-structured Fe 3 O 4 or MnO and fcc-structured metals. The relaxivity values of the Au-MnO and Au-Fe 3 O 4 nanoparticles were similar to those of the MnO and Fe 3 O 4 nanoparticles, respectively. Au-Fe 3 O 4 heterostructured nanoparticles conjugated with two kinds of 12-base oligonucleotide sequences were able to sense a complementary 24-mer sequence, causing nanoparticle aggregation. This hybridization-mediated aggregation was detected by the overall size increase indicated by dynamic light scattering data, the red shift of the surface plasmon band of the Au component, and the enhancement of the signal intensity of the Fe 3 O 4 component in T 2 - weighted magnetic resonance imaging. Introduction Colloidal nanoparticles have been extensively utilized in various technological areas because of their unique size- dependent electronic, optical, and magnetic properties. 1 In particular, different kinds of nanoparticles have been extensively used in biomedical applications. 2 For example, various magnetic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents, magnetic drug-delivery vehicles, and in bioseparations. 3 Our group recently developed a new T 1 MRI contrast agent using MnO nanoparticles. 4 Semiconductor nano- particles have been used as fluorescent probes for cell labeling, tracking, and imaging. 5 Au nanoparticles derivatized with oligonucleotides can sense complementary DNA (cDNA) strands, as detected by color changes resulting from the shift of surface plasmon resonance peaks between isolated and aggregated nanoparticles. 6 Recently, various heterostructured nanoparticles composed of two different kinds of materials have been synthesized, 7 merging the properties of the individual materials and creating the potential for new multifunctional biomedical applications. For example, Sun and co-workers synthesized heterostructured nanoparticles composed of ferrite and Au 8a or Ag 8b and used them as a dual MRI and optical- imaging probe 8c in a magneto-optical application, 8b respectively. However, most of the reported syntheses of heterostructured † School of Chemical and Biological Engineering, Seoul National University. ‡ Department of Radiology, Seoul National University College of Medicine. (1) (a) Nanoscale Materials in Chemistry; Klabunde, K. J., Ed.; Wiley- Interscience: New York, 2001. (b) Nanoparticles and Nanostructured Films; Fendler, J. H., Ed.; Wiley-VCH: Weinheim, Germany, 1998. (c) Alivisatos, A. P. Science 1996, 271, 933–937. (d) Hyeon, T. Chem. Commun. 2003, 927–934. (e) Park, J.; Joo, J.; Kwon, S. G.; Jang, Y.; Hyeon, T. Angew. Chem., Int. Ed. 2007, 46, 4630–4660. (2) (a) Niemeyer, C. M.; Mirkin, C. A. Nanobiotechnology: Concepts, Applications and PerspectiVes; Wiley-VCH: Weinheim, Germany, 2004. (b) Wang, J. Small 2005, 1, 1036–1043. (3) (a) Weissleder, R.; Kelly, K.; Sun, E. Y.; Shtatland, T.; Josephson, L. Nat. Biotechnol. 2005, 23, 1418–1423. (b) Bulte, J. W. M.; Zhang, S. C.; Van Gelderen, P.; Herynek, V.; Jordan, E. K.; Duncan, I. D.; Frank, J. A. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 15256–15261. (c) Jun, Y. W.; Huh, Y. M.; Choi, J. S.; Lee, J. H.; Song, H. T.; Kim, S.; Yoon, S.; Kim, K. S.; Shin, J. S.; Suh, J. S.; Cheon, J. J. Am. Chem. Soc. 2005, 127, 5732–5733. (d) Gu, H.; Ho, P. L.; Tsang, K. W. T.; Wang, L.; Xu, B. J. Am. Chem. Soc. 2003, 125, 15702–15703. (e) Xu, C.; Xu, K.; Gu, H.; Zhong, X.; Guo, Z.; Zheng, R.; Zhang, X.; Xu, B. J. Am. Chem. Soc. 2004, 126, 3392–3393. (f) Xu, C.; Xu, K.; Gu, H.; Zheng, R.; Liu, H.; Zhang, X.; Guo, Z.; Xu, B. J. Am. Chem. Soc. 2004, 126, 9938–9939. (4) Na, H. B.; Lee, J. H.; An, K.; Park, Y. I.; Park, M.; Lee, I. S.; Nam, D.-H.; Kim, S. T.; Kim, S.-H.; Kim, S.-W.; Lim, K.-H.; Kim, K.-S.; Kim, S.-O.; Hyeon, T. Angew. Chem., Int. Ed. 2007, 46, 5397–5401. (5) (a) Dubertret, B.; Skourides, P.; Norris, D. J.; Noireaux, V.; Brivanlou, A. H.; Libchaber, A. Science 2002, 298, 1759–1762. (b) Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H. Nat. Mater. 2005, 4, 435–446. (c) Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan, G.; Wu, A. M.; Gambhir, S. S.; Weiss, S. Science 2005, 307, 538–544. (d) Klostranec, J. M.; Chan, W. C. W. AdV. Mater. 2006, 18, 1953–1964. (6) (a) Taton, T. A.; Mirkin, C. A.; Letsinger, R. L. Science 2000, 289, 1757–1760. (b) Nam, J. M.; Thaxton, C. S.; Mirkin, C. A. Science 2003, 301, 1884–1886. Published on Web 10/25/2008 10.1021/ja805311x CCC: $40.75  2008 American Chemical Society J. AM. CHEM. SOC. 2008, 130, 15573–15580 9 15573