Metalloporphyrin-indomethacin conjugates as new photosensitizers for photodynamic therapy.

Abstract

Photodynamic therapy (PDT) is a promising cancer treatment approach with the advantages of low toxicity and noninvasive characteristics. In this study, a series of metalloporphyrin-indomethacin conjugates tethered with poly(ethylene glycol) (PEG) chains were prepared and characterized. The singlet oxygen production of the conjugates was evaluated through 2', 7'-dichlorofluorescin (DCFH) method. Because of the heavy atom effect, the metal porphyrin complexes exhibited the higher singlet oxygen (1O2) quantum yield than that of free base porphyrin. The order of 1O2 yield of the synthesized porphyrins was PtPor > PdPor > ZnPor > Por. The MTT assay using HeLa cells verified the low cytotoxicity of porphyrin-indomethacin conjugates in the dark. Upon irradiation, the platinated porphyrin (PtPor) showed the highest therapeutic activity among these conjugates, probably due to its high efficiency of 1O2 generation. The cellular uptake and subcellular localization of the conjugates were further evaluated through a confocal laser scanning microscope. The results showed that the conjugates were primarily localized in the lysosomes of HeLa cells.