Department of Natural Sciences, Lebanese American University, Chouran, Beirut 1102-2801, Lebanon.
Dalton Trans. 2018 Apr 3;47(14):4959-4967. doi: 10.1039/C8DT00140E.
Copper is an earth-abundant and a biologically essential metal that offers a promising alternative to noble metals in photochemistry and photobiology. In this work, a series of sterically encumbered Cu(i) bis-phenanthroline complexes were investigated for their use in photochemotherapy (PCT). It was found that Cu(dsbtmp)2+ [dsbtmp = 2,9-disec-butyl-3,4,7,8-tetramethyl-1,10-phenanthroline] (compound 3), which possessed the longest excited state lifetime, exhibited significant in vitro photocytotoxicity on A375 (human malignant melanoma) and A549 (human lung carcinoma) cell lines. Fluorescence imaging demonstrated the significant uptake and localization of compound 3 in a perinuclear fashion. A comet assay indicated the induction of DNA damage in the dark. The DNA breaks were significantly amplified upon photoactivation. The light-induced enhancement of cytotoxicity was associated with the formation of reactive oxygen species (ROS), a known intermediate in photodynamic therapy (PDT). This successful demonstration of photocytotoxicity using long-lived cuprous phenanthroline paves the way to exploit this class of photosensitizers for PDT applications.
铜是一种在地壳中含量丰富且对生物体必不可少的金属，它在光化学和光生物学领域为替代贵金属提供了有前景的选择。在这项工作中，研究了一系列空间位阻较大的 Cu(i) 双菲啰啉配合物在光化疗（PCT）中的应用。研究发现，具有最长激发态寿命的 Cu(dsbtmp)2+ [dsbtmp = 2,9-二仲丁基-3,4,7,8-四甲基-1,10-菲啰啉]（化合物 3）对 A375（人恶性黑色素瘤）和 A549（人肺癌）细胞系表现出显著的体外光细胞毒性。荧光成像表明，化合物 3 以核周方式显著摄取和定位。彗星试验表明，暗处理时会诱导 DNA 损伤。光激活后，DNA 断裂明显放大。光诱导增强的细胞毒性与活性氧（ROS）的形成有关，ROS 是光动力疗法（PDT）中的已知中间产物。使用长寿命的亚铜菲啰啉成功证明了光细胞毒性，为利用这一类光敏剂进行 PDT 应用铺平了道路。
