Trimodal Ni(II) Complex of Natural Coumarin: Enhanced Lung Cancer Therapy through Chemo, Photodynamic, and Photothermal Approaches under Red and NIR Light

We report four square planar Ni­(II) complexes [Ni­(B)­(L)] (S1–S4), where B is 1,10-phenanthroline (S1, S2) or dipyrido­[3,2-a:2’,3′-c]­phenazine (S3, S4) and L is the dianionic form of catechol (S1, S3) or esculetin (S2, S4). These complexes absorb in the red and NIR region (600–850 nm) and remain stable under thermal, photo, and dark conditions. S4 showed strong phototoxicity under combined 660 and 808 nm light via singlet oxygen generation and local hyperthermia, with IC50 = 0.9 μM in A549 lung cancer cells, but negligible toxicity to HEK-293 normal kidney cells. Mechanistic studies revealed apoptosis, G2/M arrest, and ROS-mediated cell damage. Molecular docking studies showed significant interaction of S4 with HER2 and Cyclin D1 proteins, suggesting apoptosis via inhibition. To the best of our knowledge, this is the first report of a first-row transition metal complex for application in trimodal lung cancer therapy within the clinical phototherapeutic window.