Fluorescein-Functionalized Iridium(III) Complexes as Dual-Mode Type I Photosensitizers for Hypoxia-Tolerant Photodynamic and X-ray-Induced Therapy
Language English Country United States Media print-electronic
Document type Journal Article
- MeSH
- Fluorescein * chemistry pharmacology MeSH
- Photochemotherapy * MeSH
- Photosensitizing Agents * pharmacology chemistry chemical synthesis MeSH
- Iridium * chemistry pharmacology MeSH
- Coordination Complexes * pharmacology chemistry chemical synthesis MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis MeSH
- Reactive Oxygen Species metabolism MeSH
- X-Rays MeSH
- Drug Screening Assays, Antitumor MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Fluorescein * MeSH
- Photosensitizing Agents * MeSH
- Iridium * MeSH
- Coordination Complexes * MeSH
- Antineoplastic Agents * MeSH
- Reactive Oxygen Species MeSH
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 (O2•-) 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, PS1, outperforms existing systems by efficiently generating both singlet oxygen O2(1Δg) 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.
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