Ir(III) complexes for photo-activated mitochondrial G-quadruplex damage against cisplatin-resistant cancer cells

Lung cancer is the leading cause of cancer-related deaths worldwide, and chemotherapy resistance poses a major challenge in its clinical treatment. Photodynamic therapy offers a promising therapeutic strategy; however, existing photosensitizers often lack clear targets and are prone to causing toxic side effects. In this work, we constructed mitochondrial-targeted chiral iridium complexes (Λ-Ir and Δ-Ir). These complexes selectively bind to mitochondrial G-quadruplexes. Upon light irradiation, the chiral photosensitizers selectively oxidize and damage mitochondrial G-quadruplexes, thereby impairing mitochondrial function. This ultimately induces autophagy and ferroptosis in drug-resistant lung cancer cells, effectively overcoming tumor resistance.