2,3‐bis((4‐(Pyridin‐2‐yl)‐1H‐1,2,3‐Triazol‐1‐yl)methyl) Quinoxaline Based Cyclometalated Binuclear Ir (III) Complex for Photodynamic Therapy in Triple Negative Breast Cancer Cell

Herein, we have developed a novel 2,3-bis ((4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl) methyl) quinoxaline based binuclear cyclometalated Iridium (III) complex (CIr₂L) for TNBC treatment. The complex has high protein binding affinity (K_HSA=0.362×10⁶ M^-1) and high DNA binding affinity (K_b=0.92×10⁶ M^-1). The complex exhibited best efficiency as a Type II PDT agent due to its ability to induce ¹O₂ generation. The low dark cytotoxicity, high phototoxicity (IC₅₀=2.3±0.8 μM, PI=31.3) and selectivity (selectivity factor>50-fold over normal HEK-293 cells) of complex CIr₂L in MDA-MB-231 TNBC cell line makes it well-suited for PDT. The DCFDA comparison study conducted in MDA-MB-231 cells under light and dark conditions demonstrated significant ROS generation with light exposure. JC-1 staining revealed a substantial disruption in mitochondrial membrane potential (MMP). The mechanism of cell death was evaluated using an annexin V-FITC/PI flow cytometric assay, confirming a higher percentage of early apoptotic cells under light exposure. Mechanistically, this type of electropositive binuclear complex is being selectively transported to cancer cell membrane through serum albumin and depleted the GSH level by the generation of ROS in presence of light leading to DNA photocleavage followed by apoptosis.