Evaluation of the effects of newly synthesized metallophthalocyanines on breast cancer cell lines with photodynamic therapy

Abstract

In this study, the new phthalonitrile derivative 3-(4-(3-oxobutyl)phenoxy)phthalonitrile (1) and its non-peripheral metallophthalocyanine derivatives [zinc (2), copper (3), cobalt (4), manganese (5), gallium (6), and indium (7)] were synthesized. The newly synthesized phthalocyanines were characterized by standard spectroscopic methods, such as FT-IR, ¹H NMR, UV-Vis, fluorescence spectroscopies, and MALDI-TOF spectrometry. Aggregation behaviors of the novel phthalocyanines were investigated by UV-Vis spectroscopy. The effect of pH change on the electronic and emission spectra of the newly synthesized phthalocyanine derivatives was studied in THF media. The electronic spectra of the new zinc (2), copper (3), and cobalt (4) phthalocyanines exhibited bathochromic shifts in acidic pH values due to the presence of monoprotonated forms. Surprisingly, the same effect was not observed for manganese (5) and indium (7) phthalocyanines. On the other hand, gallium (6) showed a slight red-shifted band with the addition of HCl to the medium. Also, it was determined that the synthesized zinc (2) and gallium (6) phthalocyanines had a selective phototoxic effect on the MCF-7 breast cancer cell line compared to the MCF-10A healthy breast cell line. The IC₅₀ values of zinc (2) and gallium (6) phthalocyanines were determined for MCF-7 and MCF-10A cell lines. The IC₅₀ values of MCF-7 for compounds 2 and 6 were found to be 1.721 ± 0.4 μg mL⁻¹ and 7.406 ± 0.32 μg mL⁻¹, respectively. The IC₅₀ values of MCF-10A for phthalocyanines 2 and 6 were found to be 48.90 ± 0.69 μg mL⁻¹ and 14.77 ± 1.09 μg mL⁻¹, respectively. In the LDH (lactate dehydrogenase)-ELISA study, the LDH levels that formed on a cellular basis after the application were measured, and it was observed that the cells were directed towards apoptosis. In addition, it was observed that cancer cells underwent more apoptosis than healthy cells as a result of this application with cell-cycle and dead cell kits performed by flow cytometry. This research shows that non-peripheral substituted gallium and zinc phthalocyanine derivatives (2 and 6) can be suitable photosensitizers for the photodynamic treatment of breast cancers.