In Vivo Monitoring of Gold Nanorods and Tissue Damage Mediated with their Photothermal Effect
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In Vivo Monitoring of Gold Nanorods and Tissue Damage Mediated with their Photothermal Effect Takuro Niidome1,2,3, Yasuyuki Akiyama1, Kohei Shimoda1, Takahito Kawano1, Takeshi Mori1,2, Yoshiki Katayama1,2 and Yasuro Niidome1 1 Department of Applied Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 8190395, Japan. 2 Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan. 3 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, 332-0012, Japan. ABSTRACT Gold nanorods have a strong surface plasmon band at the near infrared region. The absorbed light energy is then converted to heat. Since near infrared light can penetrate deeply into tissue, gold nanorods are expected to be used as a contrast agent for bioimaging using the near infrared light and photosensitizers for photothermal therapy. The surface plasmon bands of intravenously injected the gold nanorods were directly monitored from the mouse abdomen by using a spectrophotometer equipped with an integrating sphere. The absorbance at 900 nm from PEG5,000-modified gold nanorods immediately increased after injection and reached a plateau. The injection of phosphatidylcholine-modified gold nanorods also increased the absorbance at 900 nm, but the absorbance decreased single exponentially with a 1.3-min half-life. To demonstrate photothermal tumor therapy, the PEG-modified gold nanorods were directly injected into subcutaneous tumors in mice, then, near infrared laser light was irradiated to the tumor. After the treatment, significant suppression of tumor growth was observed. INTRODUCTION Gold nanorods, rod-shaped gold nanoparticles, show two surface plasmon bands corresponding to the transverse and longitudinal surface plasmon bands in the visible (~ 520 nm) and the near infrared regions (~ 900 nm), respectively [1-3]. The near infrared region is ideally suited for in vivo imaging and therapy due to minimum light absorption of intrinsic chromophores, hemoglobin (< 650 nm), and water (> 900 nm), indicating maximal penetration of light into tissues [4]. In addition, since the adsorbed light energy is converted to heat, the nanorods are expected to be used as a nanodevice for photothermal therapy. Gold nanorods are prepared in a micellar solution of hexadecyltrimethylammonium bromide (CTAB) which stabilizes the colloidal dispersion of nanorods [1]. To remove cytotoxic CTAB from the solution and provide biocompatible nanorods, phosphatidylcholine (PC) [5] and polyethylene glycol (PEG) [6,7] were employed as biocompatible stabilizers for the gold nanorods. The PEG5,000modified gold nanorods showed long lasting circulation after intravenous injection [7]. In this study, first, to assess application of gold nanorods as a probe for near infrared bioimaging, we attempted to detect the surface plasmon band of gold nanorods in a mouse using a spectrophotometer, and achieved real-time monitoring of the photoabsorption of gold nanorods. Second, to assess potential as a photothermal device for photother
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