Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario, Canada.
Chem Commun (Camb). 2019 Aug 15;55(67):9971-9974. doi: 10.1039/c9cc03942b.
Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.
光动力疗法（PDT）是一种临床认可的癌症治疗方法，它利用光、氧和光敏剂来产生局部活性氧（ROS）。由于 ROS 的寿命很短，因此人们认为光敏剂在细胞中的位置是决定 PDT 结果的关键因素。为了探索光敏剂与 DNA 直接结合的效果，我们将一种众所周知的 DNA 结合染料 DAPI 转化为光敏剂。与天然 DAPI 不同，Br-DAPI 在受到照射后会产生 ROS。我们证明，只有当 Br-DAPI 与 DNA 结合时，ROS 才会有效地诱导双链 DNA 断裂。在癌细胞（A549）中，Br-DAPI 会导致快速的光依赖性细胞死亡。这项工作支持了设计与靶细胞 DNA 具有高亲和力的光敏剂的想法，这可能会使 PDT 更有效。
