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Cancer phototherapy by CO releasing terpyridine-based Re(I) tricarbonyl complexes via ROS generation and NADH oxidation
Dalton Transactions ( IF 3.5 ) Pub Date : 2024-07-25 , DOI: 10.1039/d4dt01309c
Rajesh Kushwaha 1 , Aarti Upadhyay 2 , Sukanta Saha 3 , Ashish Kumar Yadav 1 , Arpan Bera 2 , Arnab Dutta 3 , Samya Banerjee 1
Affiliation  

Here, we have synthesized and characterized three visible light responsive terpyridine based-Re(I)-tricarbonyl complexes; [Re(CO)3(ph-tpy)Cl] (Retp1), [Re(CO)3(an-tpy)Cl] (Retp2), and [Re(CO)3(py-tpy)Cl] (Retp3) where ph-tpy = 4′-phenyl-2,2′:6′,2″-terpyridine; an-tpy = 4′-anthracenyl-2,2′:6′,2″-terpyridine, py-tpy = 4′-pyrenyl-2,2′:6′,2″-terpyridine. The structures of Retp1 and Retp2 were confirmed from the SC-XRD data, indicating distorted octahedral structures. Unlike traditional PDT agents, these complexes generated reactive oxygen species (ROS) via type I and type II pathways and oxidized redox crucial NADH (reduced nicotinamide adenine dinucleotide) upon visible light exposure. Retp3 showed significant mitochondrial localization and demonstrated photoactivated anticancer activity (IC50 ∼ 2 µM) by inducing ROS-mediated cell death in cancer cells selectively (photocytotoxicity Index, PI > 28) upon compromising mitochondrial function in A549 cells. Their diagnostic capabilities were ultimately assessed using clinically relevant 3D multicellular tumor spheroids (MCTs).

中文翻译:


CO 通过 ROS 生成和 NADH 氧化释放基于三联吡啶的 Re(I) 三羰基复合物进行癌症光疗



在这里,我们合成并表征了三种可见光响应的三联吡啶基-Re( I )-三羰基配合物; [Re(CO) 3 (ph-tpy)Cl] ( Retp1 )、[Re(CO) 3 (ant-tpy)Cl] ( Retp2 ) 和 [Re(CO) 3 (py-tpy)Cl] ( Retp3 ) 其中 ph-tpy = 4′-苯基-2,2′:6′,2″-三联吡啶; an-tpy = 4′-蒽基-2,2′:6′,2″-三联吡啶,py-tpy = 4′-芘基-2,2′:6′,2″-三联吡啶。从 SC-XRD 数据证实了Retp1Retp2的结构,表明其为扭曲的八面体结构。与传统的 PDT 药物不同,这些复合物在可见光照射下通过I 型和 II 型途径产生活性氧 (ROS),并氧化氧化还原关键的 NADH(还原型烟酰胺腺嘌呤二核苷酸)。 Retp3显示出显着的线粒体定位,并通过损害 A549 细胞中的线粒体功能选择性地诱导癌细胞中 ROS 介导的细胞死亡(光细胞毒性指数,PI > 28)来表现出光激活抗癌活性(IC 50 ∼ 2 µM)。最终使用临床相关的 3D 多细胞肿瘤球体 (MCT) 评估了他们的诊断能力。
更新日期:2024-07-30
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