RRC ID 67461
著者 Hirohara S, Oka C, Totani M, Obata M, Yuasa J, Ito H, Tamura M, Matsui H, Kakiuchi K, Kawai T, Kawaichi M, Tanihara M.
タイトル Synthesis, Photophysical Properties, and Biological Evaluation of trans-Bisthioglycosylated Tetrakis(fluorophenyl)chlorin for Photodynamic Therapy.
ジャーナル J Med Chem
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.
巻・号 58(21)
ページ 8658-70
公開日 2015-11-12
DOI 10.1021/acs.jmedchem.5b01262
PMID 26457363
MeSH Animals Breast / drug effects Breast / pathology Breast Neoplasms / drug therapy* Breast Neoplasms / pathology Cell Line, Tumor Female Halogenation Humans Hydrocarbons, Chlorinated / chemical synthesis Hydrocarbons, Chlorinated / chemistry* Hydrocarbons, Chlorinated / pharmacokinetics Hydrocarbons, Chlorinated / therapeutic use* Mice Mice, Inbred BALB C Neoplasms / drug therapy Neoplasms / pathology Photochemotherapy Photosensitizing Agents / chemical synthesis Photosensitizing Agents / chemistry* Photosensitizing Agents / pharmacokinetics Photosensitizing Agents / therapeutic use*
IF 6.205
リソース情報
ヒト・動物細胞 T98G(RCB1954)