Phototherapeutic activity of polypyridyl ruthenium(II) complexes through synergistic action of nitric oxide and singlet oxygen

In recent years, photodynamic therapy (PDT) and gas therapy (GT) have emerged as research hotspots due to their excellent cancer treatment efficacy. By combining the advantages of both, the simultaneous and controllable release of reactive oxygen species (ROS) and nitric oxide (NO) has become a possibility. This paper describes the design of two Ru(II) complexes, [Ru(bpy)2(NFIP)](PF6)2 (Ru1, bpy = 2,2'-bipyridine, NFIP = 4-nitro-3-trifluoromethylaniline-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ru(phen)2(NFIP)](PF6)2 (Ru2, phen = 1,10-phenanthroline), through the integration of the polypyridyl ruthenium structure and a photoresponsive NO donor. The structures and purity of the complexes were confirmed by several methods, including 1H NMR, mass spectrometry, elemental analysis, high performance liquid chromatography (HPLC) and UV-Vis absorption spectra. Both complexes were demonstrated to efficiently generate singlet oxygen (1O2) (ΦΔ = 0.40 and 0.44 in phosphate buffered saline (PBS) for Ru1 and Ru2, respectively) and release NO under visible light irradiation. Upon light exposure, Ru2 exhibited significant phototoxicity against human cervical cancer HeLa cells. In vitro experiments indicated that Ru2 elevated the levels of ROS and NO in HeLa cells when exposed to light, resulting in mitochondrial impairment and caspase-mediated cell death. Overall, Ru2 proves to be a potent phototherapeutic compound, capable of producing ROS and NO, thus providing precision in cancer phototherapy.