A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer†,Dalton Transactions

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A long-lived cuprous bis-phenanthroline complex for the photodynamic therapy of cancer†
Dalton Transactions ( IF 3.5 ) Pub Date : 2018-02-27 00:00:00 , DOI: 10.1039/c8dt00140e
Cynthia Al Hageh _{1,

2,

3,

4} , Majd Al Assaad _{1,

2,

3,

4} , Zeinab El Masri _{1,

2,

3,

4} , Nawar Samaan _{1,

2,

3,

4} , Mirvat El-Sibai _{1,

2,

3,

4} , Christian Khalil _{1,

2,

3,

4} , Rony S. Khnayzer _{1,

2,

3,

4}

Affiliation

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.

中文翻译：

一种长寿命的亚铜双菲咯啉配合物，用于癌症的光动力治疗†

铜是一种富含地球的物质，也是一种生物必需金属，在光化学和光生物学中，它是贵金属的有希望的替代物。在这项工作中，研究了一系列空间受限的Cu（I）双菲咯啉配合物在光化学疗法（PCT）中的用途。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-菲咯啉]（化合物3），在A375（人类恶性黑色素瘤）和A549（人类肺癌）细胞系中表现出显着的体外光细胞毒性。荧光成像显示化合物3的大量摄取和定位以核周方式彗星试验表明在黑暗中诱导了DNA损伤。DNA断裂在光活化后被显着扩增。光诱导的细胞毒性增强与活性氧（ROS）的形成有关，活性氧是光动力疗法（PDT）的已知中间体。使用长寿命的菲咯啉亚铜成功证明了光细胞毒性，这为在PDT应用中开发此类光敏剂铺平了道路。

更新日期：2018-02-27

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