Boosting type I process of Ru(II) compounds by changing tetrazole ligand for enhanced photodynamic therapy against lung cancer.

Boosting the photosensitization type I process will enhance the phototherapy efficacy because the superoxide radicals (O) generated during type I process are more toxic than the singlet oxygen (O) in type II process. Herein, [Ru(Hdtza)(phen)][PF] (1) and [Ru(pytz)(phen)][PF] (2) (phen = 1,10-phenanthroline) based on two nitrogen-rich tetrazole ligands, di(2H-tetrazol-5-yl) amine (Hdtza) and 5-(2-pyridyl)tetrazole (Hpytz) have been developed for photodynamic therapy (PDT) against lung cancer, respectively. Nanoprecipitation was used to prepare the nanoparticles (NPs) of both compounds. [Ru(Hdtza)(phen)][PF] NPs mainly undergo an electron transfer process to generate O while [Ru(pytz)(phen)][PF] the direct energy transfer to produce O, which is responsible for the higher phototoxicity of [Ru(Hdtza)(phen)][PF] NPs (IC ~ 4.8 μg/mL) than that of [Ru(pytz)(phen)][PF] NPs (IC ~ 13.6 μg/mL) on human lung cancer cells (A549). Furthermore, in vivo study indicates that the tumor proliferation of nude mice can be effectively inhibited with the help of laser when the mice were injected with [Ru(pytz)(phen)][PF] NPs. This work may provide a simple strategy to design type I photosensitizers for enhanced photodynamic therapy.