Modulating the Phototoxicity and Selectivity of a Porphyrazine Towards Epidermal Tumor Cells by Coordination with Metal Ions

Porphyrazines (Pzs) are porphyrin derivatives that show potential application as photosensitizers for photodynamic therapy (PDT), but are still far less explored in the literature. In this work, we evaluate how the photophysics and phototoxicity of the octakis(trifluoromethylphenyl)porphyrazine (HPz) against tumor cells can be modulated by coordination with Mg(II), Zn(II), Cu(II) and Co(II) ions. Fluorescence and singlet oxygen quantum yields for the Pzs were measured in organic solvents and in soy phosphatidylcholine (PC) liposomes suspended in water. While HPz and the respective complexes with Cu(II) and Co(II) showed very low efficiency to fluoresce and to produce O, the Mg(II) and Zn(II) complexes showed significantly higher quantum yields in organic solvents. The fluorescence of these two Pzs in the liposomes was sensitive to the fluidity of the membrane, showing potential use as viscosity markers. The cytotoxicity of the compounds was tested in HaCaT (normal) and A431 (tumor) cells using soy PC liposomes as drug carriers. Despite the low O quantum yields in water, the Mg(II) and Zn(II) complexes showed IC values against A431 cells in the nanomolar range when activated with low doses of red LED light. Their phototoxicity was ca. three times higher for the tumor cells compared to the normal ones, showing promising application as photosensitizers for PDT protocols. Considering that HPz and the respective Co(II) and Cu(II) complexes were practically non-phototoxic to the cells, we demonstrate the importance of the central metal ion in the modulation of the photodynamic activity of porphyrazines.