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) |