www.afm-journal.de FULL PAPER www.MaterialsViews.com 1082 wileyonlinelibrary.com © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1082 wileyonlinelibrary.com Adv. Funct. Mater. 2011, 21, 1082–1088 Jihye Choi, Jaemoon Yang, Joseph Park, Eunjung Kim, Jin-Suck Suh, Yong-Min Huh,* and Seungjoo Haam* 1. Introduction Molecular imaging based on different nanoplatforms has been widely studied due to the potential effects on the detection and staging of cancer. The early and specific detection of cancer is critical for identifying a cancer when it is most treatable, thus greatly improving the survival rate. Recently, optical cancer imaging has emerged as a complement to radionuclide imaging techniques such as PET (positron emission tomography) and SPECT (single photon emission computed tomography) due to their convenience and non-invasiveness. In particular, the use of near-infrared (NIR) light (700 ∼1,000 nm) for optical imaging can penetrate several centimeters into tissue because hemoglobin and water, the primary absorbers of visible and infrared light, experience their lowest absorptions in the NIR region. [1] Thus NIR imaging offers a potentially non-invasive and real- time characterization of diseased tissues using optical imaging probes including quantum dots and fluorescent-dye-doped nanoparticles. Despite their widespread use, however, fluorescent dyes are easily susceptible to photobleaching, [2] and quantum dots are difficult to functionalize in a controlled manner and are potentially toxic to cells, thus posing a concern for in vitro and in vivo applications. [3] One promising approach is the assessment of gold nanorods (GNRs) as a direct NIR absorption imaging probe, because their main absorption band is located in the NIR region due to lon- gitudinal surface plasmon and because of their chemically inert behaviors under physiological conditions. [4] Glioblastoma multiform is a lethal intracranial cancer that exhibits a relentless malignant progression that is highly resistant to conventional combination therapies such as tra- ditional radiation and chemotherapy agents. [5,6] Therefore, the early detection of glioblastoma is also very crucial for effective treatment. Herein, we demonstrate a new class of NIR absorp- tion imaging probes using GNRs for the treatment of glioblas- toma. To increase the signal-to-background ratio against the targeted cancer, we modified the surfaces of the GNRs with cyclic RGD peptides (cRGD). Small peptides containing the Arg-Gly-Asp (RGD) amino acid sequence can specifically bind to α v β 3 integrin, a cell adhesion molecule highly expressed on actively angiogenic endothelium and malignant glioma cell surfaces. [7,8] In particular, optimized cyclic RGD peptides interact with integrin receptor subtypes in a more selective manner with a higher affinity than those of linear peptides. To assess the potential of the cRGD-conjugated PGNRs to serve as a smart NIR absorption image probe, we investigated the optical properties, chemical structure, biocompatibility, and binding affinity for tumor cells as well as the in vivo enhanced imaging efficacy. A conceptual scheme of the production of cRGD-conjugated GNRs is provided in Scheme 1 . Specific Near-IR Absorption Imaging of Glioblastomas Using Integrin-Targeting Gold Nanorods Molecular imaging using nanoprobes with high resolution and low toxicity is essential in early cancer detection. Here we introduce a new class of smart imaging probes employing PEGylated gold nanorods (GNRs) conjugated to cRGD for specific optical imaging of α v β 3 integrins from glioblastoma. GNRs exhibiting an optical resonance peak in the near-infrared (NIR) region were synthesized using the seed-mediated growth method. CTAB (cetyl trimethyl- ammonium bromide) bilayer on the GNRs was replaced with a biocompatible stabilizer, heterobifunctional polyethyleneglycol (COOH-PEG-SH). Further, the carboxylated GNRs (PGNRs; PEG-coated GNRs) were functionalized with cRGD using EDC-NHS chemistry to formulate cRGD-conjugated GNRs (cRGD-PGNRs) for α v β 3 integrins. In order to assess the potential of the cRGD-PGNRs as a targeted imaging probe, we investigated their optical prop- erties, biocompatibility, colloidal stability and in vitro/in vivo binding affinities for cancer cells. Consequently, cRGD-PGNRs demonstrated excellent tumor targeting ability with no cytotoxicity, as well as sufficient cellular uptake due to stable and prolonged blood circulation of cRGD-PGNRs. DOI: 10.1002/adfm.201002253 J. Choi, J. Park, E. Kim, Prof. S. Haam Department of Chemical and Biomolecular Engineering Yonsei University Seoul 120–749, Republic of Korea E-mail: haam@yonsei.ac.kr; ymhuh@yuhs.ac Prof. J. Yang, Prof. J. Suh, Prof. Y. Huh Department of Radiology Yonsei University Seoul 120–752, Republic of Korea E-mail: ymhuh@yuhs.ac Prof. J. Yang, Prof. Y. Huh, Prof. S. Haam YUHS-KRIBB Medical Convergence Research Institute Seoul 120-752, Republic of Korea