A red light-activable hetero-bimetallic [Fe(iii)–Ru(ii)] complex as a dual-modality PDT tool for anticancer therapy†

Abstract

We developed a novel red light activable hetero-bimetallic [Fe(III)–Ru(II)] complex by combining hydroxyl radical-generating Fe(III)–catecholate as a type I PDT agent and the singlet oxygen generating Ru(II)–paracymene complex as a type II PDT agent and it potentially functions as a dual-modality PDT tool for enhanced phototherapeutic applications. 2-Amino-3-(3,4-dihydroxyphenyl)-N-(1,10-phenanthrolin-5-yl)propenamide (L²) acted as a bridging linker. The single-pot synthesis of the hetero-bimetallic [Fe(III)–Ru(II)] complex was carried out through acid–amine coupling. Various photophysical assays confirmed the photo-activated production of (˙OH) radicals and (¹O₂) oxygen generation upon activation of the [Fe(III)–Ru(II)] complex with red light (600–720 nm, 30 J cm⁻²), which resulted in enhanced cytotoxicity with a photo-index of ∼45. The complex, [Fe(III)–Ru(II)], potentially bonded to the DNA through the ruthenium moiety was responsible for minimal dark toxicity. The cytotoxic potential of the complex under red light was a result of the photo-induced accumulation of reactive oxygen species through both type I and type II photodynamic therapy (PDT) mechanisms in A549 and HeLa cells, while non-cancerous HPL1D cells remained unaffected. We probed the caspase 3/7-dependent apoptosis of the complex, [Fe(III)–Ru(II)], in vitro. Overall, the hetero-bimetallic [Fe(III)–Ru(II)] complex is an ideal example of a red light activable dual-modality next-generation PDT tool for phototherapeutic anticancer therapy.