Gold nanorods for target selective SPECT/CT imaging and photothermal therapy in vivo.

The development of theranostic agents with high detection sensitivity and antitumor efficacy at low concentration is a challenging task for target selective imaging and therapy of cancers. In this study, folate-conjugated and radioactive-iodine-labeled gold nanorods (GNRs) were designed and synthesized for target selective SPECT/CT imaging and subsequent thermal ablation of folate-receptor-overexpressing cancers. Both (ortho-pyridyl) disulfide-poly(ethylene glycol)-folate and a short peptide, H(2)N-Tyr-Asn-Asn-Leu-Ala-Cys-OH, were conjugated on the surface of the GNRs through thiol chemistry. The tyrosine in the peptide sequence was introduced for radioactive-iodine labeling through an iodine-tyrosine interaction. The labeling efficiency of radioactive iodine was more than 99%. Radiochemical stability tests on iodine-125-labeled GNRs in human serum showed that 91% of the iodine-125 remained intact on the GNRs after incubation for 24 h. In vitro and in vivo results in this study confirmed the potential utility of folate-conjugated and iodine-125-labeled GNRs as smart theranostic agents. This type of platform may also be useful for the targeted SPECT/CT imaging and photothermal therapy of inflammatory diseases such as atherosclerosis and arthritis, in which folate-receptor-overexpressing macrophages play pivotal roles.

[1]  H. Dai,et al.  Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. , 2008, Journal of the American Chemical Society.

[2]  A. Koch,et al.  Macrophages and their products in rheumatoid arthritis , 2007, Current opinion in rheumatology.

[3]  P. Low,et al.  Folate receptor alpha as a tumor target in epithelial ovarian cancer. , 2008, Gynecologic oncology.

[4]  I. Tabas Macrophage death and defective inflammation resolution in atherosclerosis , 2010, Nature Reviews Immunology.

[5]  M. Tomayko,et al.  Determination of subcutaneous tumor size in athymic (nude) mice , 2004, Cancer Chemotherapy and Pharmacology.

[6]  Victor C Yang,et al.  Cancer theranostics: the rise of targeted magnetic nanoparticles. , 2011, Trends in biotechnology.

[7]  Xueding Wang,et al.  125I-labeled gold nanorods for targeted imaging of inflammation. , 2011, ACS nano.

[8]  C. Murphy,et al.  Anisotropic metal nanoparticles: Synthesis, assembly, and optical applications. , 2005, The journal of physical chemistry. B.

[9]  Quan-Yong Luo,et al.  Incremental Value of 131I SPECT/CT in the Management of Patients with Differentiated Thyroid Carcinoma , 2008, Journal of Nuclear Medicine.

[10]  M. Béhé,et al.  Radioiodination of monoclonal antibodies, proteins and peptides for diagnosis and therapy , 2002, Nuklearmedizin.

[11]  P. Low,et al.  Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. , 2005, Analytical biochemistry.

[12]  C. Murphy,et al.  Quantitation of metal content in the silver-assisted growth of gold nanorods. , 2006, The journal of physical chemistry. B.

[13]  Jinwoo Cheon,et al.  Chemical design of nanoparticle probes for high-performance magnetic resonance imaging. , 2008, Angewandte Chemie.

[14]  G. Gazelle,et al.  Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. , 2000, AJR. American journal of roentgenology.

[15]  N. Alazraki,et al.  The role of single-photon emission computed tomography and SPECT/computed tomography in oncologic imaging. , 2011, Seminars in oncology.

[16]  M. Lorberboym,et al.  Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a parathyroid adenoma. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  P. Libby,et al.  Activatable Magnetic Resonance Imaging Agent Reports Myeloperoxidase Activity in Healing Infarcts and Noninvasively Detects the Antiinflammatory Effects of Atorvastatin on Ischemia-Reperfusion Injury , 2008, Circulation.

[18]  Michael J Sailor,et al.  Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. , 2009, Cancer research.

[19]  J. Schnitzer,et al.  Iodine-125 radiolabeling of silver nanoparticles for in vivo SPECT imaging , 2010, International journal of nanomedicine.

[20]  Ralph Weissleder,et al.  Arthritis imaging using a near-infrared fluorescence folate-targeted probe , 2005, Arthritis research & therapy.

[21]  Hongwei Liao and,et al.  Gold Nanorod Bioconjugates , 2005 .

[22]  E. Coronado,et al.  The Optical Properties of Metal Nanoparticles: The Influence of Size, Shape, and Dielectric Environment , 2003 .

[23]  Y. Nishiyama,et al.  Clinical usefulness of fusion of 131I SPECT and CT images in patients with differentiated thyroid carcinoma. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  Yu Shin Kim,et al.  Effects of gold nanorod concentration on the depth-related temperature increase during hyperthermic ablation. , 2011, Small.

[25]  Yongdoo Choi,et al.  Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo. , 2011, ACS nano.

[26]  Prashant K. Jain,et al.  Noble Metals on the Nanoscale: Optical and Photothermal Properties and Some Applications in Imaging, Sensing, Biology, and Medicine , 2009 .

[27]  R. Wendt,et al.  Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Yan Dai,et al.  Freestanding palladium nanosheets with plasmonic and catalytic properties. , 2011, Nature nanotechnology.

[29]  P. Low,et al.  Folate-targeted therapeutic and imaging agents for cancer. , 2009, Current opinion in chemical biology.

[30]  Jerry S. H. Lee,et al.  Magnetic nanoparticles in MR imaging and drug delivery. , 2008, Advanced drug delivery reviews.