MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.
The Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen, 361102, P. R. China.
Dalton Trans. 2024 Aug 6;53(31):12917-12926. doi: 10.1039/d4dt01665c.
The fast-moving field of photodynamic therapy (PDT) has provided fresh opportunities to expand the potential of metallodrugs to combat cancers in a light-controlled manner. As such, in the present study, a series of cyclometalated Ir(III) complexes modified with a tetrazine functional group (namely, Ir-ppy-Tz, Ir-pbt-Tz, and Ir-dfppy-Tz) are developed as potential two-photon photodynamic anticancer agents. These complexes target mitochondria but exhibit low toxicity towards HLF primary lung fibroblast normal cells in the dark. When receiving a low-dose one- or two-photon PDT, they become highly potent towards A549 lung cancer cells (with IC values ranging from 24.0 nM to 96.0 nM) through the generation of reactive oxygen species (ROS) to induce mitochondrial damage and subsequent apoptosis. Our results indicated that the incorporation of tetrazine with cyclometalated Ir(III) matrices would increase the singlet oxygen (O) quantum yield () and, meanwhile, enable a type I PDT mechanism. Ir-pbt-Tz, with the largest two-photon absorption (TPA) cross-section ( = 102 GM), shows great promise in serving as a two-photon PDT agent for phototherapy.
光动力学疗法（PDT）是一个快速发展的领域，为扩展金属药物的潜力以实现光控方式治疗癌症提供了新的机会。有鉴于此，在本研究中，开发了一系列带有四嗪官能团的环金属化 Ir(III) 配合物（即 Ir-ppy-Tz、Ir-pbt-Tz 和 Ir-dfppy-Tz），作为潜在的双光子光动力抗癌剂。这些配合物靶向线粒体，但在黑暗中对 HLF 原代肺成纤维细胞正常细胞的毒性较低。当接受低剂量的单光子或双光子 PDT 时，它们通过产生活性氧（ROS）来诱导线粒体损伤和随后的细胞凋亡，对 A549 肺癌细胞具有很高的效力（IC 值范围为 24.0 nM 至 96.0 nM）。我们的结果表明，将四嗪与环金属化 Ir(III) 基质结合会增加单线态氧（O ）量子产率（），同时使 PDT 机制为 I 型。Ir-pbt-Tz 的双光子吸收（TPA）截面（ = 102 GM）最大，有望成为双光子 PDT 光疗剂。
