Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, P. R. China.
Key Laboratory of Organo-Pharmaceutical Chemistry of Jiangxi Province, Gannan Normal University, Shiyuan South Road, Ganzhou 341000, P. R. China.
Biomater Sci. 2021 Jul 13;9(14):4843-4853. doi: 10.1039/d1bm00128k.
Iridium(iii) complexes are potent candidates for photodynamic therapy (PDT), but some key drawbacks still hamper clinical translation, such as poor operability in the phototherapeutic window, high dark toxicity, and low reactive oxygen species (ROS) production efficiency. In this work, a near-infrared phosphorescent Ir(iii) complex conjugated to a xanthene dye, NIR-Ir-XE, is reported with highly favourable properties for mitochondria-targeted imaging and cancer phototherapy. The generation of the triplet excited state of a xanthene moiety endows the NIR-Ir-XE to form singlet oxygen (1O2) for use as a photodynamic therapy agent after irradiation with visible light. Compared with the xanthene-free Ir(iii) counterpart (NIR-Ir-bpy), the xanthene-modified cyclometalated Ir(iii) photosensitizer NIR-Ir-XE exhibits higher 1O2 generation efficiency, negligible dark toxicity and a better therapeutic effect. Importantly, a clear correlation between cell death and intracellular generation of 1O2 derived from NIR-Ir-XE after light irradiation was demonstrated. The corresponding in vivo photo-antitumor performance was further demonstrated to be effective in tumor-bearing mice. The observed properties of NIR-Ir-XE qualify it as a promising PDT agent.
铱（III）配合物是光动力疗法（PDT）的有力候选物，但一些关键的缺点仍然阻碍了其临床转化，例如在光疗窗口中的操作性能差、暗毒性高和活性氧（ROS）生成效率低。在这项工作中，报道了一种近红外磷光铱（III）配合物与吖啶染料的共轭物，即 NIR-Ir-XE，它具有用于线粒体靶向成像和癌症光疗的优异性质。吖啶部分的三重态激发态的产生赋予了 NIR-Ir-XE 在可见光照射后形成单线态氧（1O2）的能力，可作为光动力治疗剂使用。与无吖啶的铱（III）对应物（NIR-Ir-bpy）相比，吖啶修饰的环金属化铱（III）光敏剂 NIR-Ir-XE 表现出更高的 1O2 生成效率、可忽略的暗毒性和更好的治疗效果。重要的是，在光照后，从 NIR-Ir-XE 衍生的细胞死亡与细胞内 1O2 的产生之间存在明确的相关性。还进一步证明了其在荷瘤小鼠中的体内光抗肿瘤性能是有效的。NIR-Ir-XE 的观察到的性质使其成为一种有前途的 PDT 剂。
