title: Synthesis, Photophysical Properties, and Biological Evaluation of trans-Bisthioglycosylated Tetrakis(fluorophenyl)chlorin for Photodynamic Therapy.
abstract: trans-Bisthioglycosylated tetrakis(fluorophenyl)chlorin (7) was designed as a powerful photodynamic therapy (PDT) photosensitizer based on the findings of our systematic studies. We show here that the trans-bisthioglycosylated structure of 7 enhanced its uptake by HeLa cells and that the chlorin ring of 7 increased the efficiency of reactive oxygen species generation under the standard condition of our photocytotoxicity test. The versatility of 7 in PDT treatment was established using weakly metastatic B16F1 melanoma cells, metastatic 4T1 breast cancer cells, the RGK-1 gastric carcinoma mucosal cell line, and three human glioblastoma cell lines (U87, U251, and T98G). The pharmacokinetics of 7 in mice bearing 4T1 breast cancer cells showed a high tumor-to-skin concentration ratio (approximately 60) at 24 h after intraperitoneal injection. The PDT efficacy of 7 in vivo was approximately 250-times higher than that of mono-l-aspartyl chlorin e6 (9) in mice bearing 4T1 breast cancer cells.
authors.affiliation: Department of Chemical and Biological Engineering, Ube National Collage of Technology , 2-14-1 Tokiwadai, Ube 755-8555, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Hirohara
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Chio
authors.initials: C
authors.lastname: Oka
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Totani
authors.affiliation: Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi , Kofu 400-8510, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Obata
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Yuasa
authors.affiliation: Faculty of Medicine, University of Tsukuba , 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Faculty of Medicine, University of Tsukuba , 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Faculty of Medicine, University of Tsukuba , 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Kakiuchi
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawaichi
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology , Takayama 8916-5, Ikoma, Nara 630-0192, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tanihara
mesh_terms: D000818:Animals; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D054879:Halogenation; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D006843:Hydrocarbons, Chlorinated; D017319:Photosensitizing Agents