Photodynamic activity of indolenine-based aminosquaraine cyanine dyes: Synthesis and in vitro photobiological evaluation

Abstract The synthesis and characterization of several indolenine-based symmetrical squaraine dyes is herein reported. These compounds, possessing different amine groups bound to the squaric ring, display strong absorption within the so-called “phototherapeutic window”, have high singlet oxygen generation ability and high stability in the presence of radiation. Moreover, their potential as photosensitizers was evaluated in vitro by a photodynamic activity test in several tumor (Caco-2, MCF-7 and PC-3) and non-tumor (NHDF and N27) cell lines. Light-emitting diode systems emitting radiation at wavelengths close to those of maximum dye absorption were constructed and used in the in vitro assays. Of these, the dye with the unsubstituted four-membered central ring exhibited the most relevant photodynamic properties, with an interesting selectivity for PC-3 cells when compared to the normal human cell line (NHDF) being observed. Aminosquaraine dyes bearing amino and ethanolamino groups, despite showing marked cytotoxicity compared to the zwitterionic dye, produced some phototherapeutic effect. Flow cytometry, using propidium iodide as a viability staining, demonstrated that this zwitterionic dye induces death within the range of 4–24 h after exposure to light. Our study also showed that this dye does not accumulate preferentially in cell's mitochondria. Although in different extents, the squaraine dyes involved in this work presented promising in vitro results as photosensitizers.