Porphyrazine metal complexes as photosensitizers and local viscosity sensors for personalized photodynamic therapy

Abstract

Despite the high efficiency, selectivity and good tolerance of photodynamic therapy (PDT), the task of creating an “ideal” photosensitizer (PS) remains unresolved. The search for new drugs is a key link in improving the technology of anticancer therapy. In addition to the need to search for the “ideal” PS, characterized by increased selectivity of accumulation in the tumor and, accordingly, the direction of the therapeutic effect, the PDT method is limited by the lack of the possibility of adequate and timely adjustment of the light dose delivered to the tumor, depending on the response of the irradiated tissue.
The aim of our study was to study porphyrazine metal complexes as potential agents for personalized PDT conducting the ability to monitor its effectiveness in real time.
We studied tetra (thiophen-3-yl) tetracyanoporphyrazinates of iron, copper, and tetra (benzothiophen-2-yl) tetracyanoporphyrazinates (PZ) of iron, copper, and palladium.
We have shown the presence of intense absorption and fluorescence peaks in the studied PZ metal complexes for the biological transparency window. PZ metal complexes with benzothiophene substituents in the peripheral environment of the macrocycle were shown to absorb light and emit fluorescence in a longer wavelength region of the spectrum than it was shown for metal complexes with thiophene substituents. In addition, we registered a significant increase in the quantum yield and fluorescence lifetime of all studied PZ metal complexes with an increase in the viscosity of the medium in the experiment on alcohol-glycerol mixtures. So the studied metal complexes are shown to belong to the class of fluorescent molecular rotors, characterized by high viscosity sensitivity of fluorescence parameters.
The studied PZ metal complexes are characterized by intense accumulation of A431 in human epidermoid carcinoma tumor cells. Recorded high photodynamic indices (the ratio of the concentrations of half-maximum inhibition during incubation in the "dark" and under photoinduced exposure) in an experiment on cell cultures for PZ of iron, copper and palladium with a benzothiophene group.
An increase in the lifetime of the excited state of PZ metal complexes in A431 cells under photodynamic exposure was shown. Such changes were not recorded in non-irradiated cells. It was shown that with an increase in the dose of photodynamic exposure, an increase in the lifetime of the excited state of PZ metal complexes in cells occurs. The data obtained, most likely, indicate an increase in local intracellular viscosity in cells subjected to photodynamic action.
Thus, the studies carried out demonstrate the promise of using PZ metal complexes for solving the problems of personalized PDT, in which the state of tumor cells can be controlled by changes in intracellular viscosity, which can be estimated by measuring the fluorescence lifetime.
The work is supported by the Scholarship of the President of the Russian Federation No.SP-1609.2021.4

Speaker

Natalia Shilyagina
Lobachevsky University, Nizhny Novgorod
Россия

Discussion

Ask question