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

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 (O) 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 (Ir(N^C)(N^N) in which N^C = 2-phenylpyridine and N^N = 1-(2-benzimidazolyl)-β-carboline) displays a remarkably high phototoxicity index (PI = IC in the dark/IC in light) of >833 against human lung carcinoma A549 cells. Further studies show that -mediated PDT induces caspase-dependent apoptosis through lysosomal damage. The pH-responsive phosphorescence of complex can be utilized to monitor the lysosomal integrity upon PDT, which provides a reliable and convenient method for 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.