Photodynamic therapy holds great promise as a non-invasive
anticancer
tool against drug-resistant cancers. However, highly effective, non-toxic,
and reliable photosensitizers with operability under hypoxic conditions
remain to be developed. Herein, we took the advantageous properties
of COUPY fluorophores and cyclometalated Ir(III) complexes to develop
novel PDT agents based on Ir(III)-COUPY conjugates with the aim of
exploring structure–activity relationships. The structural
modifications carried out within the coumarin scaffold had a strong
impact on the photophysical properties and cellular uptake of the
conjugates. All Ir(III)-COUPY conjugates exhibited high phototoxicity
under green light irradiation, which was attributed to the photogeneration
of ROS, while remaining non-toxic in the dark. Among them, two hit
conjugates showed excellent phototherapeutic indexes in cisplatin-resistant
A2780cis cancer cells, both in normoxia and in hypoxia, suggesting
that photoactive therapy approaches based on the conjugation of far-red/NIR-emitting
COUPY dyes and transition metal complexes could effectively tackle
in vitro acquired resistance to cisplatin.