Synthesis and Characterization of Photosensitizer-conjugated Gold Nanorods for Photodynamic/Photothermal Therapy

광역학적/광열치료 응용을 위한 광증감제가 결합한 골드 나노로드의 합성 및 특성분석

  • Choi, Jongseon (Graduate School of Energy Science and Technology, Chungnam National University) ;
  • Kim, So Yeon (Graduate School of Energy Science and Technology, Chungnam National University)
  • 최종선 (충남대학교, 에너지과학기술대학원) ;
  • 김소연 (충남대학교, 에너지과학기술대학원)
  • Received : 2016.09.25
  • Accepted : 2016.10.11
  • Published : 2016.12.10


Recently, photodynamic and photothermal therapies have received increasing attention as an effective cancer treatment. In this study, a gold nanorod (AuNR) colloidal solution was synthesized as a hyperthermia agent for photothermal therapy and also modified with photosensitizer (PS) for photodynamic therapy. PEG (polyethylene glycol) and FA (folic acid) ligand were also introduced into AuNR for the long circulation in human body and efficient targeting of cancer cells, respectively and AuNRs were modified with FA-PEG and poly-${\beta}$-benzyl-L-aspartate (PBLA) block copolymers through a 3,4-dihydroxy hydrocinnamic acid (HCA) linker. A series of AuNRs with various aspect ratios were synthesized by controlling the feeding ratio of $AgNO_3$. The physicochemical property and morphology of synthesized AuNR100 and FA-PEG-$P(Asp)_{50}$-HCA-AuNR100 were analyzed by UV-visible spectrophotometer, $^1H$ NMR, XPS measurements, TEM. The surface modified AuNR carrier with biocompatibility could be applied for the effective diagnosis as well tumor phototherapy.


Supported by : 한국연구재단


  1. Y. Tabata, Y. Murakami, and Y. Ikada, Tumor accumulation of poly(vinyl alcohol) of different sizes after intravenous injection, J. Control. Release, 50, 123-133 (1998).
  2. E. M. Liversidege, G. G. Liversidege, and E. R. Cooper, Nanosizing: a formulation approach for poorly-water-soluvle compounds, Eur. J. Pharm. Sci., 18, 113-120 (2003).
  3. W. M. Sharman, C. M. Allen, and J. E. van Lier, Photodynamic therapeutics: basic principles and clinical applications, Drug Discov. Today, 4, 507-517 (1999).
  4. H. Youn, K. W. Kang, J. K. Chung, and D. S. Lee, Nanomedicine: Drug delivery systems and nanoparticle targeting, Nucl. Med. Mol. Imaging., 42, 337-346 (2008).
  5. P. Couvreur and C. Vauthier, Polyalkylcyanoacrylate nanoparticles as drug carrier: present state and perspectives, J. Control. Release, 17, 187-198 (1991).
  6. T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, and Q. Peng, Photodynamic therapy, J. Natl. Cancer Inst., 90, 889-905 (1998).
  7. M. H. Gold, Introduction to photodynamic therapy: early experience, Dermatol. Clin., 25, 1-4 (2007).
  8. D. E. Dolmans, D. Fukumura, and R. K. Jain, Photodynamic therapy for cancer, Nat. Rev. Cancer, 3, 380-387 (2003).
  9. A. J. Gormley, K. Greish, A. Ray et al., Gold nanorod mediated plasmonic photothermal therapy: a tool to enhance macromolecular delivery, Int. J. Pharm., 30, 315-318 (2011).
  10. G. V. Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas, Cance Res., 69, 3892-3900 (2009).
  11. A. P. Castano, P. Mroz, and M. R. Hamblin, Photodynamic therapy and anti-tumour immunity, Nat. Rev. Cancer, 6, 535-545 (2006).
  12. R. Ackroyd, C. Kelty, N. Brown, and M. Reed, The history of photodetection and photodynamic therapy, Photochem., 74, 656-669 (2001).
  13. S. K. Baek, Clinical application of nanotechnology, Korean J. Otorhinolaryngol-Head Neck Surg., 54, 185-191 (2011).
  14. H. Ma, P. M. Bendix, and L. B. Oddershede, Large-scale orientation dependent Heating from a single irradiated gold nanorod, Nano Lett., 12, 3954-3960 (2012).
  15. S. E. Lohse and C. J. Murphy, The quest for shape control: A history of gold nanorod synthesis, Chem. Mater., 25, 1250-1261 (2013).
  16. B. S. Jang, J. Y. Park, C. H. Tung, I.-H. Kim, and Y. Choi, Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo, ACS Nano., 2, 1086-1094 (2011).
  17. K. Y. Lin, A. F. Bagley, A. Y. Zhang, D. L. Karl, S. S. Yoon, and S. N. Bhatia, Gold nanorod photothermal therapy in a genetically engineered mouse model of soft tissue sarcoma, Nano Life, 1, 277-287 (2010).
  18. G. F. Paciotti, L. Myer, D. Weinreich et al., Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv., 11, 169-183 (2004).
  19. Q. L. Li and Y. H. Cao, Preparation and characterization of gold nanorods. In: Dr. Orhan Yalci (eds.). Nanorods, 159-178, Rijeka, Croatia (2012).
  20. T. K. Sau and C. J. Murphy, Seeded high yield synthesis of short Au nanorods in aqueous solution, Langmuir, 20, 6414-6420 (2004).
  21. L. Zhao, T. H. Kim, J. C. Ahn, H. W. Kim, and S. Y. Kim, Highly efficient "theranostics" system based on surface-modified gold nanocarriers for imaging and photodynamic therapy of cancer, J. Mater. Chem. B., 1, 5806-5817 (2013).
  22. X. Huang, S. Neretina, and M. A. El-sayed, Gold nanorods: from synthesis and properties to biological and biomedical applications, Adv. Mater., 21, 4880-4910 (2009).
  23. C. J. Murphy, L. B. Thompson, D. J. Chernak, J. A. Yang, S. T. Sivapalan, S. P. Boulos, J. Huang, A. M. Alkilany, and P. N. Sisco, Gold nanorod crystal growth: from seed-mediated synthesis to nanoscale sculpting, Curr. Opin. Colloid Interface Sci., 16, 128-134 (2011).
  24. B. Nikoobakht and M. A. El-sayed, Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method, Chem. Mater., 15, 1957-1962 (2003).
  25. M. A. Liu, P. Guyot-Sionnest, Mechanism of silver(I)-assisted growth of gold nanorods and bipyramids. J. Phys. Chem. B., 109, 22192-22200 (2005).
  26. M. R. Langille, M. L. Personick, J. Zhang, and C. A. Mirkin, Defining rules for the shape evolution of gold nanoparticles, J. Am. Chem. Soc., 134, 14542-14554 (2012).
  27. X. Huang, I. H. El-sayed, W. Qian, and M. A. El-Sayed, Cancer cell imaging and phtothermal therapy in the near-infrared region by using gold nanorods, Langmuir, 26, 6066-6070 (2010).
  28. B. Isomaa, J. Reuter, and B. M. Diupsund, The subacute and chronic toxicity of cetyltrimethylammounium bromide (CTAB), a cationic surfactant, in the rat, Arch. Toxicol., 35, 91-96 (1979).
  29. P. C. Ray, H. T. Yu, and P. P. Fu, Toxicity and environmental risks of nanomaterials: challenges and future needs, J. Environ. Sci. Health C, 27, 1-35 (2009).
  30. Z. Huang, A review of progress in clinical photodynamic therapy, Technol. Cancer Res. Treat., 4, 283-293 (2005).
  31. J. P. Celli, B. Q. Spring, L. Rizvi, C. L. Evans, K. S. Samkoe, S. Verma, B. W. Pogue, and T. Hasan, Imaging and photodynamic therapy: mechanisms, monitoring, and optimization, Chem. Rev., 110, 2795-2838 (2010).
  32. K. Fujiwara and T. Watanabe, Effects of hyperthermia, radiotherapy and thermoradiotherapy on tumor microvascular permeability, Pathol. Int., 40, 79-84 (2008).
  33. D. P. O'Neal, L. R. Hirsch, N. J. Halas, J. D. Payne, and J. L. West, Photo-thermal tumor ablation in mice using near infrared- absorbing nanoparticles, Cancer Lett., 209, 171-176 (2004).