Cyclometalated iridium(iii) complexes as lysosome-targeted photodynamic anticancer and real-time tracking agents†

Abstract

We report the rational design and photodynamic anticancer mechanism studies of iridium( iii) complexes with pH-responsive singlet oxygen ( ¹O ₂) production and lysosome-specific imaging properties.

Abstract

Stimuli-activatable photosensitizers (PSs) are highly desirable for photodynamic therapy (PDT) to selectively demolish tumor cells. On the other hand, lysosomes are emerging as attractive anticancer targets. Herein, four cyclometalated iridium( iii)–β-carboline complexes with pH-responsive singlet oxygen ( ¹O ₂) production and lysosome-specific imaging properties have been designed and synthesized. Upon visible light (425 nm) irradiation, they show highly selective phototoxicities against cancer cells. Notably, complex 2 ([Ir(N^C) ₂(N^N)](PF ₆) in which N^C = 2-phenylpyridine and N^N = 1-(2-benzimidazolyl)-β-carboline) displays a remarkably high phototoxicity index (PI = IC ₅₀ in the dark/IC ₅₀ in light) of >833 against human lung carcinoma A549 cells. Further studies show that 2-mediated PDT induces caspase-dependent apoptosis through lysosomal damage. The pH-responsive phosphorescence of complex 2 can be utilized to monitor the lysosomal integrity upon PDT, which provides a reliable and convenient method for in situ monitoring of therapeutic effect and real-time assessment of treatment outcome. Our work provides a strategy for the construction of highly effective multifunctional subcellular targeted photodynamic anticancer agents through rational structural modification of phosphorescent metal complexes.

Notes

†Electronic supplementary information (ESI) available: Synthesis and characterization data, biological studies, supplementary figures, tables and movies. CCDC 883318 and 1061866. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc01955a