ABSTRACT We report the in vitro cell test and in vivo animal test results of titanium oxide nanotubes (TiO2 NTs) as a potential therapeutic agent used for cancer thermotherapy in combination with near-infrared (NIR) laser. The in vitro cell test results show that both the cells exposed to NIR laser without TiO2 NTs treatment and the cells treated with TiO2 NTs but not with NIR irradiation had cell viabilities higher than 96%. Combination of these two techniques, however, shows cell viability less than 1%. The cell death rate strongly depended on the concentration of TiO2 NTs. Also, the cell deaths were mostly due to necrosis but partly due to late apoptosis. The in vivo animal test results show that tumor cells can be completely destroyed without nearly giving damage to surrounding healthy cells by an injection of an adequate amount of TiO2 NTs/NaCl suspension and a subsequent single continuous laser treatment at a moderately low laser illumina-tion intensity for the exposure time optimized for the tumor size. These results suggest that TiO2 NTs can be effectively utilized as a therapeutic agent for cancer thermotherapy due to their excellent photothermal property and high bio-compatibility.
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nullC. Hong, J. Kang, J. Lee, H. Zheng, S. Hong, D. Lee and C. Lee, "Photothermal Therapy Using TiO2 Nanotubes in Combination with Near-Infrared Laser," Journal of Cancer Therapy, Vol. 1 No. 2, 2010, pp. 52-58. doi: 10.4236/jct.2010.12009.
 V. P. Zharov, E. N. Galitovskaya, C. Johnson and T. Kelly, “Synergistic Enhancement of Selective Nanophoto Thermolysis with Gold Nanoclusters: Potential for Cancer Therapy,” Lasers in Surgery and Medicine, Vol. 37, No. 3, 2005, pp. 219-226.
 X. Huang, I. H. El-Sayed and M. A. El-Sayed, “Cancer Cell Imaging and Photothermal Therapy in the Near- Infrared Region by Using Gold Nanorods,” Journal of the American Chemical Society, Vol. 128, No. 6, 2006, pp. 2115- 2120.
 L. R. Hirsch, R. J. Stafford, J. A. Baukson, S. R. Sershen, B. Rivera, R. E. Price, J. D. Hazle, N. J. Halas, J. L. West, “Nanoshell-Mediated Near-Infrared Thermal Therapy of Tumors under Magnetic Resonance Guidance,” Proceed-ings of the National Academy of Sciences USA, Vol. 100, No. 23, 2003, pp. 13549-11554.
 J. Chen, B. Wiley, Z.-Y. Li, D. Campbell, F. Saeki, H. Cang, L. Au, J. Lee, X. Li and Y. Xia, “Gold Nanocages: Engineering their Structure for Biomedical Applications,” Advanced Materials, Vol. 17, No. 18, 2005, pp. 2255- 2261.
 S. Link and M. A. El-Sayed, “Shape and Size Dependence of Radiative, Non-Radiative and Photothermal Properties of Gold Nanocrystals,” International Reviews in Physical Chemistry, Vol. 19, No. 3, 2000, pp. 409-453.
 N. W. S. Kam, M. O. Connell, J. A. Wisdom and H. Dai, “Carbon Nanotubes as Multifunctional Biological Trans-porters and Near-Infrared Agents for Selective Cancer Cell Destruction,” Proceedings of the National Academy of Sciences USA, Vol. 102, 2005, pp. 11600-11605.
 C. Lee, H. Kim, C. Hong, M. Kim, S. S. Hong, D. H. Lee and W. I. Lee, “Porous Silicon as an Agent for Cancer Thermotherapy Based on Near-Infrared Light Irradiation,” Journal of Materials Chemistry, Vol. 18, No. 40, 2008, pp. 4790-4795.
 S. N. Goldberg, G. S. Gazelle and P. R. Mueller, “Thermal Ablation Therapy for Focal Malignancy,” American Journal of Roentgenology, Vol. 174, No. 2, 2000, pp. 323-331.
 A. Jordan, K. Maier-Hauff, P. Wust and M. Johaunsen, “Nanotechnologies for the Life Sciences” In: C. Kumar, Ed., Nanomaterials for Cancer Therapy, Wiley-VCH, Weinheim, 2006, pp. 242-258.
 C. Yao, G. Balasundaram and T. Webster, “Use of Ano-dized Titanium in Drug Delivery Applications,” Materials Research Society Symposium Proceedings, Boston, Vol. 951E, 2007, pp. 28-29.
 C. von Wilmowsky, S. Bauer, R. Lutz, M. Meisel, F. W. Neukam, T. Toyoshima, P. Schmuki, E. Nkenke and K. A. Schlegel, “In Vivo Evaluation of Anodic TiO2 Nanotubes: An Experimental Study in the Pig,” Journal of Biomedical Materials Research, Vol. 89B, No.1, 2009, pp. 165- 171.
 Y. T. Sul, C. B. Johansson, Y. Jeong and T. Albrektsson, “The Electrochemical Oxide Growth Behaviour on Tita-nium in Acid and Alkaline Electrolytes,” Medical Engi-neering and Physics, Vol. 23, No. 5, 2001, pp. 329-346.
 Y. M. Zhang, P. Bataillon-Linez, P. Huang, Y. M. Zhao, Y. Han, M. Traisnel, K. W. Xu and H. F. Hildebrand, “Surface Analyses of Micro-Arc Oxidized and Hydro-thermally Treated Titanium and Effect on Osteoblast Be-havior,” Journal of Biomedical Materials Research, Vol. 68A, No. 2, 2004, pp. 383-391.
 K. Sasaki, K. Asanuma, K. Johkura, T. Kasuga, Y. Okouchi, N. Ogiwara, S. Kubota, R. Teng, L. Cui and X. Zhao, “Ultrastructural Analysis of TiO2 Nanotubes with Photodecomposition of Water into O2 and H2 Implanted in the Nude Mouse,” Annals of Anatomy, Vol. 188, No. 2, 2006, pp. 137-142.
 J. M. Jang, S. J. Park, G. S. Choi, T. Y. Kwon and K. H. Kim, “Chemical State and Ultra-Fine Structure Analysis of Biocompatible TiO2 Nanotube-Type Oxide Film Formed on Titanium Substrate,” Metal and Materials International, Vol. 14, No. 4, 2008, pp. 457-464.
 A. Garcia-Ripoll, A. M. Amat, A. Argues, R. Vicente, M. M. Ballesteros Martin, J. A. Sanchez Perez, I. Oller and S. Malato, “Confirming Pseudomonas Putida as a Reliable Bioassay for Demonstrating Biocompatibility Enhancement by Solar Photo-Oxidative Processes of a Biorecalcitrant Effluent,” Journal of Hazadous Materials, Vol. 162, No. 2-3, 2009, pp. 1223-1227.
 V. Zwilling, M. Aucouturier and E. Darque-Ceretti, “Anodic Oxidation of Titanium and TA6V Alloy in Chromic Media. An Electrochemical Approach,” Elec-trochimica Acta, Vol. 45, No. 6, 1999, pp. 921-929.
 Laws and Regulations on animal Experiments, Ministry of Health & Welfare, Seoul, 19 June 2009.
 W. R. Chen, R. L. Adams, K. E. Bartels and R. E. Nord-quist, “Chromophore-Enhanced in Vivo Tumor Cell De-struction Using an 808 Nm Diode Laser,” Cancer Letters, Vol. 94, No. 2, 1995, pp. 125-131.