A Cyclometalated IrIII Complex as a Lysosome-Targeted Photodynamic Therapeutic Agent for Integrated Imaging and Therapy in Cancer Cells

Abstract

Organelle-targeted photosensitizers (PSs) having luminescence properties are potential theranostic agents for simultaneous luminescence imaging and photodynamic therapy. Herein, we report a water-soluble luminescent cyclometalated Ir^III complex, Ir-Bp-Ly, as a lysosome-targeted theranostic probe. Ir-Bp-Ly exhibits exceptional photophysical properties, with good triplet-state quantum yield (0.90), singlet oxygen generation quantum yield (0.71 at pH 4), and long lifetime (1.47 μs). Interestingly, Ir-Bp-Ly localizes mostly in lysosomes due to the presence of morpholine units, suggesting its potential use as a lyso-tracker. Ir-Bp-Ly displays a notable PDT effect in C6 glioma cells, efficiently generating reactive oxygen species owing to close proximity between the energy levels of its triplet state and those of molecular oxygen (³ O₂ ). The mechanism of cell death has been studied through caspase-3/7 and flow cytometry analyses, which clearly established the apoptotic pathway.

Keywords: apoptosis; cell imaging; lysosomes; singlet oxygen; theranostic agents.