Palladium porphyrin complexes for photodynamic cancer therapy: effect of porphyrin units and metal†
Photodynamic therapy (PDT) has been extensively explored for malignant tissue treatment. In this work, we successfully synthesized and characterized a series of porphyrin compounds by connecting porphyrin units with alkyl chains, which were then coordinated with palladium to yield related metal complexes, named Pd-Monopor, Pd-Dipor, and Pd-Tripor, respectively. The generation of reactive oxygen species (ROS) of six porphyrin compounds was investigated by the dichlorofluorescein (DCFH) method. As expected, the palladium porphyrin complexes showed the higher efficiency of ROS generation relative to free base porphyrins, probably due to the heavy atom effect. Remarkably, the efficiency of ROS generation increased with the number of porphyrin units in the photosensitizers. The order of ROS generation efficiency of the synthesized porphyrins was Pd-Tripor > Tripor > Dipor > Pd-Monopor > Pd-Dipor > Monopor. MTT assay suggested the good biocompatibility of the synthesized photosensitizers in the dark. Upon light irradiation, the palladium porphyrin complex exhibited higher therapeutic activity than free base porphyrin. The half-maximal inhibitory concentration (IC50) of Tripor and Pd-Tripor under light irradiation was calculated to be 18.2 and 9.6 μM, respectively. The cellular uptake and subcellular localization experiments indicated that Tripor was mainly localized in the lysosomes of cancer cells.