Bichromophoric ruthenium(<scp>ii</scp>) bis-terpyridine-BODIPY based photosensitizers for cellular imaging and photodynamic therapy

Abstract

Two multichromophoric homoleptic ruthenium(II) complexes [Ru(tpy-BODIPY)₂]Cl₂ (complexes 1 and 2, tpy = 4-phenyl-2,2:6,2-terpyridine, BODIPY = boron-dipyrromethene) were prepared, characterized and their phototherapeutic activity and bioimaging properties were studied. The complexes having structural similarity differ only by a phenylethynyl linker, and its overall influence on their physicochemical and photobiological behavior was evaluated. The terpyridine-BODIPY ligand L¹ was structurally characterized by X-ray crystallography. The complexes showed intense absorption near 500 nm (<i>ε</i>: ∼1.5 × 10⁵ M^-1 cm^-1 in DMSO), have a high singlet oxygen quantum yield (<i>Φ</i>_Δ: ∼0.6 in DMSO), and displayed low photobleaching thus making them suitable for PDT applications. The complexes showed high DNA binding affinity and induced DNA damage on light activation <i>via</i> multiple types of ROS production. Confocal laser scanning microscopy experiments revealed their incorporation in the cancer cells and complex 1 predominantly accumulated in lysosomes. The complexes displayed a significant PDT effect in cancerous cells with visible light activation with a high photocytotoxicity index (PI) value in HeLa cells. Both type-I and type-II photosensitization processes were involved in the PDT effect. The photodynamic action of complex 2 initiated cellular apoptosis. Finally, their diagnostic potential was evaluated against clinically relevant 3D multicellular tumor spheroids (MCTs).