Avaliação de fotossensibilizadores fenotiazínicos para terapia fotodinâmica

Abstract

Photodynamic therapy (PDT) is a promising option for treating cancer, benign diseases and infections by microorganisms. PDT consists of the use of a photosensitizing agent (PS) that selectively localizes in the target tissue and, upon activation by exposure to visible radiation, generates species that cause cellular damage and consequently cell death. Methylene blue (MB) is a photosensitizer of the phenothiazine’s class that has been extensively studied in in vitro, in vivo and clinical models. Other phenothiazines such as Azure A, Azure B may also have biological activity for PDT, but there is lack of information regarding their photophysical, photochemical and photobiological properties. In this context, the objective of this project was to compare the photodynamic efficiency of the Methylene Blue, Azure A and Azure B in an in vitro tumor cells model (HeLa). The IC50 of the photosensitizers were determined in the dark and with irradiation, besides the cellular incorporation of the compounds and the singlet oxygen production quantum yield and the aggregation in water and phosphate buffer saline. The IC50 values in the dark and irradiated were used to calculate the PS effectivity, and it increases in the series Azure A, Azure B and Methylene Blue. No difference was observed in singlet oxygen production and cell uptake for Methylene Blue is lower than Azure A and Azure B. The dimer to monomer ratio shows that aggregation increases in the series Methylene Blue, Azure B and Azure A. Thus, comparing the photosensitizers studied, Methylene blue is the most efficient photosensitizer for photodynamic therapy, followed by Azure B and Azure A. The phenothiazine effectivity is aggregation dependent and to reach increase effectivity is important to develop new compounds with lower aggregation or new formulations to reduce aggregation.