Photodynamic Therapy Combined with Drug-Delivery System and Fiber Optics Technology Yuji MORIMOTO, Nobuhiro NISHIYAMA and Kazunori KATAOKA Photodynamic therapy PDThas already been established as anti-cancer therapy. However, topical irradiation of light by a conventional optical fiber results in an insu cient PDT e ect in case that cancer proliferates multifocally and/or di usely. Hence, we have developed a novel fiber probe that provides homogenous light irradiation on the mucosa of hollow organs. Widespread and homogenous irradiation in the mucosa of the bladder was achieved using the newly developed fiber probe. PDT using a combination of the fiber probe and a newly developed drug-delivery system DDStype photosensitizer based on micelle technology enhanced the anti-tumor e ect without bladder shrinking. Key words: rat, bladder tumor, drug-delivery system DDS, micelle, dendrimer, homogenous light irradiation photodynamic therapy; PDT CD-R 1 PDT 1 O 2 reactiveoxygen species; ROS PDT 1996 2 2 3 PDT DDS 1. PDT 1 O 2 ROS 3598513 32E-mail: moyan@ndmc.ac.jp 1130033 731 41 11 2012 561 15
2-4 PDT 1 1 O 2 1 O 2 nm 4 1 nm 5 1 4 2 PDT PDT 6 1 PDT p 1 O 2 562 16 1 2. DDSDDS DDS 78 DDS enhanced permeability and retentionepr 4 PDT 2. 1 DDS DDS 1 O 2 9, 10 2
PDT 680 nm DPc DPc DPc/m 2 11, 12 DPc poly ethylene glycol-polyl-iysinepeg-pll 1 O 2 EPR 4 DDS 2. 2 DDS 2 DDS EPR 13 3 3 EPR 4 DPc/m 30 nm EPR 13 3 nm 5 nm EPR 11 2. 3 3 41 11 2012 563 17
DPc/m (7.1 mg/kg) DPc (1.9 mg/kg) P (0.34 mg/kg) Control A549 100 J/cm 2 4DDS PDT DPc/m DPcP DPc DPc/m PDT DPc PDT 50 1 50 DPc/m A549 PDT 8 1 2 11 4DPc/m DPc/m 11 5 DPc/m DDS PDT 3. PDT PDT 100200 mw/ cm 2 10 PDT 60 J/cm 2 5 564 18
6HIFiP HIFiP DDS / 23 DPc/m 10 DDS PDT DDS 41 11 2012 3. 1 14 6 37015 mm 40015 mm 45020 mm 1.51 555NA 0.41 565 19
DPc Ultrasound imaging 7 homogenous irradiation fiber probes: HIFiP HIFiP 71.3 flat cleaved end 31.3 2 HIFiP 70 2 6 3. 2 DPc DPc/m HIFiP PDT PDT AY27 35 24 566 20 4 HIFiP 150 mw/cm 2 DPc/m PDT PDT 3 1 PDT 7 DDS PDT PDT
PDT PDT 1 1997. 2A. Obana, Y. Gohto, K. Kaneda, S. Nakajima, T. Takemura and T. Miki: Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10, Lasers Surg. Med., 24 1999209222. 3Y. N. Hsiang, M. T. Crespo, L. S. Machan, R. D. Bower and M. E. Todd: Photodynamic therapy for atherosclerotic stenoses in Yucatan miniswine, Can. J. Surg., 37 1994148152. 4Y. Matsumura and H. Maeda: A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res., 46 198663876392. 5M. D. Carbonare and M. A. Pathak: Skin photosensitizing agents and the role of reactive oxygen species in photoaging, J. Photochem. Photobiol. B, 14 1992105124. 6 J. I. Harty, M. Amin, T. J. Wieman, M. T. Tseng, D. Ackerman and W. Broghamer: Complications of whole bladder dihematoporphyrin ether photodynamic therapy, J. Urol., 141 1989 13411346. 7A. S. Derycke and P. A. de Witte: Liposomes for photodynamic therapy, Adv. Drug Delivery Rev, 56 20041730. 8C. F. van Nostrum: Polymeric micelles to deliver photosensitizers for photodynamic therapy, Adv. Drug Delivery Rev., 56 2004916. 9W. D. Jang, N. Nishiyama, G. D. Zhang, A. Harada, D. L. Jiang, S. Kawauchi, Y. Morimoto, M. Kikuchi, H. Koyama, T. Aida and K. Kataoka: Supramolecular nanocarrier of anionic dendrimer porphyrins with cationic block copolymers modified with polyethylene glycol to enhance intracellular photodynamic e cacy, Angew Chem. Int. Ed. Engl., 44 2005419423. 10Y. Li, W. D. Jang, N. Nishiyama, A. Kishimura, S. Kawauchi, Y. Morimoto, S. Miake, T. Yamashita, M. Kikuchi, T. Aida and K. Kataoka: Dendrimer generation e ects on photodynamic e cacy of dendrimer porphyrins and dendrimer-loaded supramolecular nanocarriers, Chem. Mater., 19 200755575562. 11N. Nishiyama, Y. Nakagishi, Y. Morimoto, P. S. Lai, K. Miyazaki, K. Urano, S. Horie, M. Kumagai, S. Fukushima, Y. Cheng, W. D. Jang, M. Kikuchi and K. Kataoka: Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine, J. Controlled Release, 133 2009245251. 12S. Herlambang, M. Kumagai, T. Nomoto, S. Horie, S. Fukushima, M. Oba, K. Miyazaki, Y. Morimoto, N. Nishiyama and K. Kataoka: Disulfide crosslinked polyion complex micelles encapsulating dendrimer phthalocyanine directed to improved e ciency of photodynamic therapy, J. Controlled Release, 155 2011449457. 13N. Nishiyama, Y. Morimoto, W. D. Jang and K. Kataoka: Design and development of dendrimer photosensitizer-incorporated polymeric micelles for enhanced photodynamic therapy, Adv. Drug Delivery Rev, 61 2009327338. 14K. Miyazaki, Y. Morimoto, N. Nishiyama, Y. Maekawa, W. Z. Hu, K. Nakatate, K. Kaneda, N. Shinomiya and K. Kataoka: A novel homogeneous irradiation fiber probe for whole bladder wall photodynamic therapy, Lasers Surg. Med., 44 2012413 420. 2012 7 3 41 11 2012 567 21