trans-Bisglycoconjugation is an Efficient and Robust Architecture for PDT Photosensitizers Based on 5,10,15,20-Tetrakis(pentafluorophenyl)porphyrin Derivatives

• Published in: Bulletin of the Chemical Society of Japan 2013-11, Vol.86 (11), p.1295-1308
• Main Authors: Hirohara, Shiho, Sharyo, Kohei, Kawasaki, Yuji, Totani, Masayasu, Tomotsuka, Ayumi, Funasako, Ryota, Yasui, Nobutaka, Hasegawa, Yasuchika, Yuasa, Junpei, Nakashima, Takuya, Kawai, Tsuyoshi, Oka, Chio, Kawaichi, Masashi, Obata, Makoto, Tanihara, Masao
• Format: Article
• Language: English
• ISSN: 0009-2673; 1348-0634
• DOI: 10.1246/bcsj.20130131

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-H22SGlc) 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). UV–vis 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 trans-bisglycoconjugated TFPP derivatives support the conclusion that trans-bisglycoconjugation is a highly efficient and robust architecture for TFPP-based PDT development.