Water-soluble porphyrin photosensitizers containing electron-withdrawing and electron-donating groups for photodynamic therapy

Photodynamic therapy is used to treat a variety of cancers. In this paper, water-soluble porphyrin photosensitizers (H(2)P1 similar to H(2)P3) for photodynamic therapy were synthesized, containing three groups -CH3, -CN, and -CF3. Density functional theory is used to optimize the structure of H(2)P1-H(2)P3 and calculate the Delta E value. The smaller the value of Delta E, the more favorable the electron transfer and thus the higher activity of the porphyrin photosensitizers. Due to the electron-withdrawing groups of -CN and -CF3, H(2)P2 and H(2)P3 have lower Delta E values, higher reactive oxygen species yields compared with H(2)P1. The H(2)P2 porphyrin photosensitizers showed positive photodynamic therapeutic activity against hepatocellular carcinoma cells (HepG2) and good compatibility with human umbilical vein endothelial cells (HUVECs) by cellular anticancer activity assay. The anti-cancer mechanism of PSs was explained by living and dead cell staining experiment and intracellular reactive oxygen species experiment. PSs produced reactive oxygen species (ROS) in cancer cells under light irradiation, which induced cancer cell apoptosis.