A Red‐Emitting Benzothiazole‐Based Tridentate Iridium(III) Complex for Mitochondria‐Targeting Anticancer Therapy

Given the limitations of platinum‐based drugs in terms of toxicity and drug resistance, the development of highly efficient and low‐toxicity iridium complexes has become a focal point in anticancer research. In this study, a new tridentate iridium complex, Ir‐BTQCl , was rationally designed and synthesized, displaying red emission at 616 nm in solution with a photoluminescence quantum yield of 5.7%. The complex exhibited potent inhibitory effects across multiple tumor cell lines and demonstrated a remarkably lower IC 50 value (2.97 μM) against A549 cells than cisplatin (20.01 μM). Mechanistic studies revealed that Ir‐BTQCl primarily localizes in mitochondria, leading to a decrease in mitochondrial membrane potential (MMP), elevated reactive oxygen species (ROS) levels, G0/G1 cell‐cycle arrest, and apoptosis via the mitochondrial pathway. In an A549 tumor‐bearing mouse model, the complex achieved a tumor inhibition rate of 76.85%, significantly outperforming cisplatin (53.62%) while showing lower systemic toxicity. This study provides new insights into the development of highly efficient and low‐toxicity mitochondria‐targeted iridium‐based antitumor agents.