Photoactivated cytotoxicity induced by heterobimetallic Ru(II)-Pt(II) polypyridyl complexes in MCF-7 cells

The heterobimetallic Ru(II)-Pt(II) polypyridyl complexes [Ru(bpy)₂(BPIMBp)PtCl₂]²⁺ (3) and [Ru(phen)₂(BPIMBp)PtCl₂]²⁺ (4) with their parent complexes [Ru(bpy)₂BPIMBp]²⁺(1) and [Ru(phen)₂BPIMBp]²⁺ (2) possessing bridging ligand (BPIMBp = 1,4′-Bis-{(2-pyridin-2-yl)-1H-imidazol-1-yl)methyl}-1,1′-biphenyl) were used for photo cytotoxicity against MCF-7 cells.The parent ruthenium complexes (complexes 1-2) exhibited a negligible increase in viscosity of DNA while hetero bimetallic Ru(II)-Pt(II) system exhibited a decrease in viscosity of DNA, indicating covalent interaction (through cis-PtCl₂ unit). The Ru(II)-Pt(II) system co-precipitated with CT-DNA confirmed the covalent binding. In electrophoretic mobility studies, the interaction of Ru(II)-Pt(II) system with plasmid DNA led to retardation of negative supercoiled form, followed by positive supercoiled migration in the dark that indicated the ability to form covalent adducts with DNA similar to cisplatin. The complexes 1-4 showed enhanced photo cleavage of plasmid DNA on blue light (~450 nm) irradiation. In a cell-based study, all the complexes exhibited photo activated cytotoxicity in MCF-7 cancer cells when exposed to visible light of ~450 nm as compared to low toxicity in absence of irradiation. Additionally, the complexes containing platinum showed induction of autophagy in GFP-LC3 expressing MCF-7 cells. Overall our study shows that the inclusion of photo sensitizer Ru(II) polypyridyl complexes to cis-PtCl₂ moiety improves anticancer properties of complexes. (author)