| RRC ID |
65924
|
| Author |
Piao W, Hanaoka K, Fujisawa T, Takeuchi S, Komatsu T, Ueno T, Terai T, Tahara T, Nagano T, Urano Y.
|
| Title |
Development of an Azo-Based Photosensitizer Activated under Mild Hypoxia for Photodynamic Therapy.
|
| Journal |
J Am Chem Soc
|
| Abstract |
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 azo-based strategy should be widely applicable to design a range of activatable photosensitizers.
|
| Volume |
139(39)
|
| Pages |
13713-13719
|
| Published |
2017-10-4
|
| DOI |
10.1021/jacs.7b05019
|
| PMID |
28872304
|
| MeSH |
Azo Compounds / chemical synthesis
Azo Compounds / chemistry
Azo Compounds / pharmacology*
Cell Hypoxia / drug effects*
Cell Line, Tumor
Humans
Photochemotherapy*
Photosensitizing Agents / chemical synthesis
Photosensitizing Agents / chemistry
Photosensitizing Agents / pharmacology*
|
| IF |
14.612
|
| Resource |
| Human and Animal Cells |
A549(RCB0098) |
