TY - JOUR
T1 - Development of an azo-based photosensitizer activated under mild hypoxia for photodynamic therapy
AU - Piao, Wen
AU - Hanaoka, Kenjiro
AU - Fujisawa, Tomotsumi
AU - Takeuchi, Satoshi
AU - Komatsu, Toru
AU - Ueno, Tasuku
AU - Terai, Takuya
AU - Tahara, Tahei
AU - Nagano, Tetsuo
AU - Urano, Yasuteru
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grant Numbers 26104509, 16H00823, and 16H05099 to K.H., JP 25104005 to T.Tahara, JP16H04102 to S.T., JP16K17859 to T.F., 16H06574 to T.U., and SENTAN, JST to K.H., and grants to K.H. from Mochida Memorial Foundation for Medical and Pharmaceutical Research. P.W. was supported by a Grant-in-Aid for JSPS Fellows.
Funding Information:
†Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan ‡Molecular Spectroscopy Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan §Ultrafast Spectroscopy Research Team, RIKEN Center for Advanced Photonics (RAP), RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan ¶PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan ⊥Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan ∥Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan #AMED CREST (Japan) Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/10/4
Y1 - 2017/10/4
N2 - Photodynamic therapy (PDT) utilizes photoirradiation in the presence of photosensitizers to ablate cancer cells via generation of singlet oxygen (1O2), but it is important to minimize concomitant injury to normal tissues. One approach for achieving this is to use activatable photosensitizers that can generate 1O2 only under specific conditions. Here, we report a novel photosensitizer that is selectively activated under hypoxia, a common condition in solid tumors. We found that introducing an azo moiety into the conjugated system of a seleno-rosamine dye effectively hinders the intersystem crossing process that leads to 1O2 generation. We show that the azo group is reductively cleaved in cells under hypoxia, enabling production of 1O2 to occur. In PDT in vitro, cells under mild hypoxia, within the range typically found in solid tumors (up to about 5% O2), were selectively ablated, leaving adjacent normoxic cells intact. This simple and practical azobased strategy should be widely applicable to design a range of activatable photosensitizers.
AB - Photodynamic therapy (PDT) utilizes photoirradiation in the presence of photosensitizers to ablate cancer cells via generation of singlet oxygen (1O2), but it is important to minimize concomitant injury to normal tissues. One approach for achieving this is to use activatable photosensitizers that can generate 1O2 only under specific conditions. Here, we report a novel photosensitizer that is selectively activated under hypoxia, a common condition in solid tumors. We found that introducing an azo moiety into the conjugated system of a seleno-rosamine dye effectively hinders the intersystem crossing process that leads to 1O2 generation. We show that the azo group is reductively cleaved in cells under hypoxia, enabling production of 1O2 to occur. In PDT in vitro, cells under mild hypoxia, within the range typically found in solid tumors (up to about 5% O2), were selectively ablated, leaving adjacent normoxic cells intact. This simple and practical azobased strategy should be widely applicable to design a range of activatable photosensitizers.
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U2 - 10.1021/jacs.7b05019
DO - 10.1021/jacs.7b05019
M3 - Article
C2 - 28872304
AN - SCOPUS:85032635044
SN - 0002-7863
VL - 139
SP - 13713
EP - 13719
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 39
ER -
