Nanotechnology-Based Photodynamic Therapy for Neovascular Disease Using a Supramolecular Nanocarrier Loaded with a Dendritic Photosensitizer Ryuichi Ideta, ²,‡ Fumitaka Tasaka, ²,‡, ∇ Woo-Dong Jang, ²,§ Nobuhiro Nishiyama, | Guo-Dong Zhang, § Atsushi Harada, ⊥ Yasuo Yanagi, ‡ Yasuhiro Tamaki, ‡ Takuzo Aida, # and Kazunori Kataoka* ,§,| Department of Ophthalmology, Graduate School of Medicine, The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Materials Science and Engineering, Graduate School of Engineering, The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Center for Disease Biology and InVestigatiVe Medicine, Graduate School of Medicine, The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Department of Applied Materials Science, Graduate School of Engineering, Osaka Prefecture UniVersity, 1-1 Gakuen-cho, Sakai, Osaka 599-8531, Japan, Department of Chemistry and Biotechnology, Graduate School of Engineering, The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, and Research & DeVelopment DiVision, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma, Nara 630-0101, Japan Received August 23, 2005; Revised Manuscript Received October 3, 2005 ABSTRACT Photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD) was evaluated using a supramolecular nanomedical device, that is, a novel dendritic photosensitizer (DP) encapsulated by a polymeric micelle formulation. The characteristic dendritic structure of the DP prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. With its highly selective accumulation on choroidal neovascularization (CNV) lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity. Photodynamic therapy (PDT) is one of the noninvasive ways of treating malignant tumors or macular degeneration. 1 PDT is based on the delivery of a photosensitizer (PS) to the target tissue after the administration of PS. Photoirradiation by appropriate laser light generates highly reactive oxygen species, such as singlet oxygen, which results in the oxidative destruction of target tissue. There are several kinds of already developed PSs for the clinical evaluation of their photo- dynamic efficacy. Most of the conventional PSs have large π-conjugation domains to extend their absorption cross sections and basically have hydrophobic characteristics. Therefore, PSs form aggregates easily, which produce the self-quenching of the excited state, in aqueous medium because of their π-π interaction and hydrophobic charac- teristics. To improve the photodynamic efficacy, the efficient delivery of PSs and high quantum yield of the singlet oxygen generation are significantly important. On the basis of this information, we have reported a dendrimer-based PS recently, dendrimer porphyrin (DP), 2-4 in which the focal porphyrin is surrounded by the third generation of poly(benzyl ether) dendrons (Figure 1a). 5 Unlike conventional PSs, the DP ensures the efficacy of singlet oxygen production even at an extremely high concentration because the dendritic * Corresponding author. Address: Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Fax +81-3-5841-7139. Tel +81-3-5841-7138. E-mail; kataoka@bmw.t.u-tokyo.ac.jp. ² Equally contributed to this work. ‡ Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo. § Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo. | Center for Disease Biology and Investigative Medicine, Graduate School of Medicine, The University of Tokyo. ⊥ Osaka Prefecture University. # Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo. 3 Santen Pharmaceutical Co., Ltd. NANO LETTERS 2005 Vol. 5, No. 12 2426-2431 10.1021/nl051679d CCC: $30.25 © 2005 American Chemical Society Published on Web 10/27/2005