Production of reactive oxygen and nitrogen species by light irradiation of a nitrosyl phthalocyanine ruthenium complex as a strategy for cancer treatment

Abstract

Production of reactive oxygen species has been used in clinical therapy for cancer treatment in a technique known as Photodynamic Therapy (PDT). The success of this therapy depends on oxygen concentration since hypoxia limits the formation of reactive oxygen species with consequent clinical failure of PDT. Herein, a possible synergistic effect between singlet oxygen and nitric oxide (NO) is examined since this scenario may display increased tumoricidal activity. To this end, the trinuclear species [Ru(pc)(pz)2{Ru(bpy)2(NO)}2](PF6)6 (pc = phthalocyanine; pz = pyrazine; bpy = bipyridine) was synthesized to be a combined NO and singlet oxygen photogenerator. Photobiological assays using at 4 × 10(-6) M in the B16F10 cell line result in the decrease of cell viability to 21.78 ± 0.29% of normal under light irradiation at 660 nm. However, in the dark and at the same concentration of compound , viability was 91.82 ± 0.37% of normal. The potential application of a system like in clinical therapy against cancer may be as an upgrade to normal photodynamic therapy.

Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen

“…Effective PSMA-targeted photoimmunotherapy has been demonstrated by Watanabe and colleagues (43) both in vitro and in vivo. Compared with antibody, low molecular weight molecules are easy to be synthesized and more cost-effective.…”

“…We used DPBF to quantify the production of singlet oxygen by each of our PDT agents by following the changes in the absorbance at 411 nm (43,44). As shown in Fig.…”

“…A diode LED light source (L690-66-60, Marubeni America Co.; see Supplementary Fig. S5C for the spectrum of the diode LED) was used to irradiate PSMA-1-IR700 at 690 nm due to its proximity to the peak of IR700 absorbance (690 nm) as reported by others (41)(42)(43). Mice were treated with irradiance of 31.8 mW/cm 2 and radiant exposure of 50 J/cm 2 .…”

“…Photo-induced singlet oxygen generation was detected by the chemical method using 1,3-diphenylisobenzofuran (DPBF) as the chemical quencher (43,44). The decay of DPBF was monitored by the absorption at 411 nm.…”

Design, Reactivity, and Biological Activity of Ruthenium Nitrosyl Complexes

“…Photochemical studies using the nitrosyl ruthenium compounds (I) and (II) could aid understanding of the biochemical mechanism involving the synergistic effect between NO and 1 O 2 (Table 8) (42,43). This could constitute a new strategy for the biological application of coordination compounds.…”