Intracellular Modulation of Excited-State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells
Intracellular Modulation of Excited-State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells
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DOI：
10.1002/anie.201411962
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发表时间：
2015-04-27
影响因子：
16.6
通讯作者：
Akkaya, Engin U.
中科院分区：
文献类型：
--
作者：
Kolemen, Safacan;Isik, Murat;Akkaya, Engin U.
活性氧物质，特别是单线态氧[O-2（a（1）Delta（g））]的光敏化产生是光动力疗法中利用的光动力作用的本质。打开/关闭单线态氧产生的能力将是非常有价值的，特别是当它与癌症相关的细胞参数相关联时。基于与系统间交叉效率相关的最新发现，我们设计了一种对称性降低的二聚体BODIPY染料，除非通过与细胞内谷胱甘肽（GSH）的反应激活，否则其作为光敏剂是无效的。该反应改变了基态和激发态的性质，从而使单线态氧的有效产生成为可能。值得注意的是，设计的光敏剂可以区分正常细胞和癌细胞中不同浓度的GSH，因此在正常细胞内作为光敏剂仍然效率低下，而在癌细胞中转化为致命的单线态氧源。这是第一次证明光敏剂的细胞内活性存在这种差异。
The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O-2(a(1) Delta(g))], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer- related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH). The reaction alters the properties of both the ground and excited states, consequently enabling the efficient generation of singlet oxygen. Remarkably, the designed photosensitizer can discriminate between different concentrations of GSH in normal and cancer cells and thus remains inefficient as a photosensitizer inside a normal cell while being transformed into a lethal singlet oxygen source in cancer cells. This is the first demonstration of such a difference in the intracellular activity of a photosensitizer.