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 (O2-) generated during type I process are more toxic than the singlet oxygen (1O2) in type II process. Herein, [Ru(Hdtza)(phen)2][PF6] (1) and [Ru(pytz)(phen)2][PF6] (2) (phen = 1,10-phenanthroline) based on two nitrogen-rich tetrazole ligands, di(2H-tetrazol-5-yl) amine (H2dtza) 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)2][PF6] NPs mainly undergo an electron transfer process to generate O2- while [Ru(pytz)(phen)2][PF6] the direct energy transfer to produce 1O2, which is responsible for the higher phototoxicity of [Ru(Hdtza)(phen)2][PF6] NPs (IC50 ~ 4.8 µg/mL) than that of [Ru(pytz)(phen)2][PF6] NPs (IC50 ~ 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)2][PF6] NPs. This work may provide a simple strategy to design type I photosensitizers for enhanced photodynamic therapy.

Naturally available hypericin undergoes electron transfer for type I photodynamic and photothermal synergistic therapy.

Naturally available compounds with bioactivity are potential candidates for cancer treatment. In this paper, we isolated hypericin (HC) from Hypericum sinense L. and investigated its antitumor activity both in vitro and in vivo. The nanoparticles (NPs) of HC were prepared by a nanoprecipitation process with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000). With light irradiation, HC NPs not only undergo efficient electron transfer to generate the superoxide radical (O2-˙) and the hydroxyl radical (OH˙) as well as energy transfer producing singlet oxygen (1O2) for photodynamic therapy (PDT), but also non-radiative decay to produce heat for photothermal therapy (PTT) with a photothermal conversion efficiency of 29.3%. This synergistic therapy, therefore, largely boosts the phototherapy efficacy of HC NPs on human cervical cancer cells (HeLa), guaranteeing a low half maximal inhibitory concentration (IC50) of only 5.6 µg mL-1. Furthermore, in vivo studies suggest that HC NPs are capable of inhibiting tumor proliferation after laser irradiation, and the main organs remain healthy, including the heart, kidneys, liver, lungs and spleen. Our results indicate that HC NPs derived from nature with excellent phototherapy efficacies are biocompatible candidates for type I PDT/PTT synergistic cancer therapy.

Photochemical property of two Ru(II) compounds based on 5-(2-pyrazinyl)tetrazole for cancer phototherapy by changing auxiliary ligand.

Ru(II) compounds are potential candidates for photodynamic therapy (PDT) and auxiliary ligands may have an impact on the property of the resulting coordination compounds. In the present study, two Ru(II) compounds based on 5-(2-pyrazinyl)tetrazole (Hpztz) and two classic auxiliary ligands, 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen) have been prepared and characterized, namely [Ru(pztz)(bipy)2][PF6] (1) and [Ru(pztz)(phen)2][PF6] (2). The nanoparticles (NPs) of the two compounds have been prepared by self-assembly in aqueous solution. In vitro MTT assay on HeLa cells show that [Ru(pztz)(phen)2][PF6] with a lower IC50 (half-maximal inhibitory concentration) of only 7.4 µg/mL is superior to that of [Ru(pztz)(bipy)2][PF6] (17.8 µg/mL) under irradiation. Meanwhile, negligible dark toxicity have been also observed for the two compounds. In addition, in vivo fluorescence imaging suggests that [Ru(pztz)(phen)2][PF6] NPs are able to target to the tumor by enhanced permeability and retention effect (EPR). Furthermore, in vivo phototherapy on nude mice demonstrate that such NPs can effectively inhibit the growth of the tumor. After treatment for 10 cycles, an obvious decrease in the tumor volume can be observed while the normal tissues, including heart, liver, spleen, lung and kidney, suffer from no damage, indicating the high phototoxicity, low dark toxicity and excellent biocompatibility of [Ru(pztz)(phen)2][PF6] NPs.