Liu Ji-Qiang, Tse Anfernee Kai-Wing, Koncošová Martina, Ruml Tomáš, Tse Yu-Chung, Liu Chuang-Jun, Zelenka Jaroslav, Kirakci Kaplan, Lang Kamil, Lee Chi-Sing, Wong Keith Man-Chung
Department of Chemistry, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen 518055, China.
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR 999077, China.
Inorg Chem. 2025 Jun 9;64(22):10894-10905. doi: 10.1021/acs.inorgchem.5c00894. Epub 2025 May 27.
The development of photosensitizers that function effectively in hypoxic environments and enable deep-tissue treatment remains a significant challenge in photodynamic therapy (PDT). Here, we report two novel Ir(III) complexes functionalized with fluorescein designed as efficient Type I photosensitizers for both light-driven PDT and X-ray-induced PDT (X-PDT). By populating the triplet state of the fluorescein ligands, these complexes facilitate the generation of reactive oxygen species (ROS) through electron transfer, producing superoxide anion radicals (O) and hydroxyl radicals (OH) under irradiation. The complexes exhibit pronounced phototoxicity against cancer cells, particularly under hypoxic conditions, where oxygen-dependent Type II photosensitizers are less effective. Remarkably, these complexes also demonstrate direct X-ray activation, offering a solution for deep-tissue cancer treatment. The lead complex, , outperforms existing systems by efficiently generating both singlet oxygen O(Δ) and free radicals, enabling synergistic Type I and II PDT effects. This work represents a major advancement in the design of oxygen-independent PDT agents by using fluorescein's triplet state, with potential applications in deep-tissue and hypoxic tumor environments.
开发在低氧环境中有效发挥作用并能实现深部组织治疗的光敏剂仍然是光动力疗法（PDT）中的一项重大挑战。在此，我们报告了两种用荧光素功能化的新型铱（III）配合物，它们被设计为用于光驱动PDT和X射线诱导的PDT（X-PDT）的高效I型光敏剂。通过填充荧光素配体的三重态，这些配合物通过电子转移促进活性氧（ROS）的生成，在照射下产生超氧阴离子自由基（O）和羟基自由基（OH）。这些配合物对癌细胞表现出显著的光毒性，特别是在低氧条件下，此时依赖氧气的II型光敏剂效果较差。值得注意的是，这些配合物还表现出直接的X射线激活作用，为深部组织癌症治疗提供了一种解决方案。先导配合物通过有效生成单线态氧O(Δ)和自由基，优于现有系统，实现了I型和II型PDT的协同效应。这项工作通过利用荧光素的三重态，在不依赖氧气的PDT剂设计方面取得了重大进展，在深部组织和低氧肿瘤环境中具有潜在应用。
