Carboxylate modified benzylidene cyclopentanone dyes for one- and two-photon excited photodynamic therapy

Benzylidene cyclopentanone dyes have high photosensitization activity and large two-photon absorption (TPA) cross-section in near infrared region. To explore their application potentials in two-photon excited photodynamic therapy (TPE-PDT), a series of carboxylate modified benzylidene cyclopentanone dyes were synthesized by varying number of carboxylate groups. Their linear and nonlinear photophysical properties, reactive oxygen yields and in vitro PDT activities were investigated systematically. The results showed that the water solubility of these dyes was significantly enhanced after introducing carboxylate groups. All dyes exhibited large TPA cross-section around 1000–1400 GM at 840 nm. In addition, they could generate both superoxide anion radical and singlet oxygen species under illumination. However, only the dye Y1 modified by one carboxylate group presented strong PDT activity to human rectal cancer 1116 cells, which indicated that moderate water–lipid amphipathy was a very important factor for PDT dyes. Finally, Y1 was proved to have large potential in TPE-PDT by in vitro experiments.

► Four water soluble benzylidene cyclopentanone dyes were synthesized by introducing carboxylate group.
► All dyes could effectively generate reactive oxygen species through both Type I and Type II mechanisms.
► Their maximum TPA cross-sections were all above 1000 GM at 840 nm.
► The dye modified by only one carboxylate group presented strong one- and two-photon excited PDT activities to human rectal cancer 1116 cells.
► The water–lipid amphipathy is a very important factor to maintain the PDT activity of a dye.