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基于 CO 释放的三吡啶钌(Ⅱ)配合物的癌症光疗:ROS 的产生和 NADH 的氧化。

Cancer phototherapy by CO releasing terpyridine-based Re(I) tricarbonyl complexes ROS generation and NADH oxidation.

机构信息

Department of Chemistry, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India.

Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India.

出版信息

Dalton Trans. 2024 Aug 13;53(32):13591-13601. doi: 10.1039/d4dt01309c.

DOI:10.1039/d4dt01309c
PMID:39078263
Abstract

Here, we have synthesized and characterized three visible light responsive terpyridine based-Re(I)-tricarbonyl complexes; [Re(CO)(ph-tpy)Cl] (Retp1), [Re(CO)(an-tpy)Cl] (Retp2), and [Re(CO)(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) 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 (IC ∼ 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).

摘要

在这里,我们合成并表征了三种对可见光有响应的三联吡啶基-Re(I)-三羰基配合物;[Re(CO)(ph-tpy)Cl](Retp1)、[Re(CO)(an-tpy)Cl](Retp2)和[Re(CO)(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'-并四苯-2,2':6',2″-三联吡啶。Retp1 和 Retp2 的结构通过 SC-XRD 数据得到确认,表明其具有扭曲的八面体结构。与传统的 PDT 剂不同,这些配合物通过可见光照射产生 I 型和 II 型途径的活性氧物种(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 显示出明显的线粒体定位,并通过在 A549 细胞中破坏线粒体功能,在可见光照射下选择性地诱导 ROS 介导的细胞死亡(细胞毒性指数,PI > 28),表现出显著的光激活抗癌活性(IC ∼ 2 µM)。最终使用临床相关的三维多细胞肿瘤球体(MCTs)评估了它们的诊断能力。

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