TY - JOUR
T1 - Trans-bisglycoconjugation is an efficient and robust architecture for PDT photosensitizers based on 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin derivatives
AU - Hirohara, Shiho
AU - Sharyo, Kohei
AU - Kawasaki, Yuji
AU - Totani, Masayasu
AU - Tomotsuka, Ayumi
AU - Funasako, Ryota
AU - Yasui, Nobutaka
AU - Hasegawa, Yasuchika
AU - Yuasa, Junpei
AU - Nakashima, Takuya
AU - Kawai, Tsuyoshi
AU - Oka, Chio
AU - Kawaichi, Masashi
AU - Obata, Makoto
AU - Tanihara, Masao
PY - 2013
Y1 - 2013
N2 - To examine the versatility of the trans-bisglycoconjugation architecture for 5,10,15,20-tetrakis(pentafluorophenyl) porphyrin (TFPP) derivative-based photodynamic therapy (PDT), 25 porphyrin derivatives bearing D-glucopyranose moieties were prepared, and their in vitro photocytotoxicities were examined. trans-Bisglycoconjugated TFPP derivatives exerted the best photocytotoxicity among TFPP derivatives in the same category, regardless of the central metal ion and the type of glycoconjugation. trans-Bisglycoconjugated free-base TFPP bearing β-D-glucopyranosylthio groups (trans- H22 SGlc) was found to be the most potent photosensitizer, not only in HeLa cells (EC50 < 5 nM), but also in highly metastatic cancer cell lines such as B16-BL6 melanoma cells (EC50 < 10 nM). UVvis and dynamic light-scattering measurements suggested that trans- bisglycoconjugated TFPP derivatives formed relatively large J-aggregates in an aqueous solution. trans-Bisglycoconjugated TFPP derivatives exhibited greater uptake by HeLa cells than those with different glycoconjugation patterns, with the exception of Zn(II) complexes. trans-Bisglycoconjugated TFPP derivatives efficiently generated hydrogen peroxide and hydroxyl radical by a type I photoreaction, while no significant differences were found in the efficiency of singlet oxygen generation by a type II photoreaction. These unique characteristics of transbisglycoconjugated TFPP derivatives support the conclusion that trans-bisglycoconjugation is a highly efficient and robust architecture for TFPP-based PDT development.
AB - To examine the versatility of the trans-bisglycoconjugation architecture for 5,10,15,20-tetrakis(pentafluorophenyl) porphyrin (TFPP) derivative-based photodynamic therapy (PDT), 25 porphyrin derivatives bearing D-glucopyranose moieties were prepared, and their in vitro photocytotoxicities were examined. trans-Bisglycoconjugated TFPP derivatives exerted the best photocytotoxicity among TFPP derivatives in the same category, regardless of the central metal ion and the type of glycoconjugation. trans-Bisglycoconjugated free-base TFPP bearing β-D-glucopyranosylthio groups (trans- H22 SGlc) was found to be the most potent photosensitizer, not only in HeLa cells (EC50 < 5 nM), but also in highly metastatic cancer cell lines such as B16-BL6 melanoma cells (EC50 < 10 nM). UVvis and dynamic light-scattering measurements suggested that trans- bisglycoconjugated TFPP derivatives formed relatively large J-aggregates in an aqueous solution. trans-Bisglycoconjugated TFPP derivatives exhibited greater uptake by HeLa cells than those with different glycoconjugation patterns, with the exception of Zn(II) complexes. trans-Bisglycoconjugated TFPP derivatives efficiently generated hydrogen peroxide and hydroxyl radical by a type I photoreaction, while no significant differences were found in the efficiency of singlet oxygen generation by a type II photoreaction. These unique characteristics of transbisglycoconjugated TFPP derivatives support the conclusion that trans-bisglycoconjugation is a highly efficient and robust architecture for TFPP-based PDT development.
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U2 - 10.1246/bcsj.20130131
DO - 10.1246/bcsj.20130131
M3 - Article
AN - SCOPUS:84888877328
VL - 86
SP - 1295
EP - 1308
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
SN - 0009-2673
IS - 11
ER -