Development of enzyme-activated photosensitizer based on intramolecular electron transfer.
Development of enzyme-activated photosensitizer based on intramolecular electron transfer.
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DOI：
10.1016/j.bmcl.2010.06.091
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发表时间：
2010-08
影响因子：
2.7
通讯作者：
T. Yogo;Y. Urano;M. Kamiya;K. Sano;T. Nagano
中科院分区：
文献类型：
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作者：
T. Yogo;Y. Urano;M. Kamiya;K. Sano;T. Nagano
光敏剂在光照时会产生细胞毒性活性氧(ROS)，但由于光照射的精度有限，在其他细胞群存在的情况下，很难去除特定类型的细胞(如肿瘤细胞)。在这里，我们报告了一种策略，通过使用酶激活的关闭/打开开关来诱导氧化应激来实现特定细胞类型的消融。在未活化的光敏剂中，氧化应激的诱导是通过分子内电子转移来抑制的。然而，靶细胞表达一种酶，该酶可以分解光敏剂的底物部分，并且激活的光敏剂会诱导氧化应激。作为概念验证，我们设计并合成了一种基于黄原烯的光敏剂TgI-βGal，它的氧化应激诱导能力在与广泛使用的基因标记β-半乳糖苷酶反应后被激活。在光照条件下，TgI-β半乳糖对LacZ阳性细胞有选择性的消融作用，而对LacZ阴性细胞无毒性。
Photosensitizers produce cytotoxic reactive oxygen species (ROS) upon light illumination, but it is difficult to ablate cells of a specific type (e.g., tumor cells) in the presence of other cell populations, because of the limited precision with which light illumination can be directed to small areas. Here, we report a strategy to achieve cell type-specific ablation by using an enzyme-activated off/on switch for oxidative stress induction. In the unactivated photosensitizer, induction of oxidative stress is quenched by intramolecular electron transfer. However, the target cells express an enzyme that hydrolyzes a substrate moiety of the photosensitizer and the activated photosensitizer induces oxidative stress. As proof of concept, we designed and synthesized a xanthene-based photosensitizer, TGI-βGal, whose oxidative stress induction ability is switched on following hydrolysis reaction with β-galactosidase, a widely used gene marker. TGI-βGal could selectively ablate lacZ-positive cells, whereas it showed no toxicity to lacZ-negative cells, upon light illumination.