Development of Porphyrin Derivatives for Theranostics

Abstract

Theranostics combining cancer diagnosis and cancer treatment is attracting attention as a field of cancer medicine. Porphyrin derivatives are used as photosensitizing molecules in cancer treatment (photodynamic therapy, PDT) and cancer diagnosis (photodynamic diagnosis, PDD). In the previous report, we developed glycosylated 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TFPP) zinc (Zn and 62 Zn) complexes as a PDT photosensitizer with positron emission tomography (PET)-tracking functionality. These complexes displayed a high cellular uptake amount, efficient photocytotoxicity, and promising PDT effect. However, they have the disadvantage of slow tumor accumulation. In this study, we synthesized TFPP zinc complexes (Zn-P) bearing two kinds of substituent groups, namely a glucose (Glc) group to improve tissue selectivity and a 2-hydroxyethanethiol (ME) group to enhance cell penetration for theranostics. We show that Zn-P(Glc) 2 (ME) 2 increased the efficiency of singlet oxygen generation under the standard condition of this photocytotoxicity test. The photocytotoxicity of Zn-P(Glc) 2 (ME) 2 was evaluated in HeLa cells, RGK-1 gastric carcinoma mucosal cells, and two human glioblastoma cells (U87 and T98G) at coincubation for 8 hours. Zn-P(Glc) 2 (ME) 2 was found to exhibit photocytotoxicity in a short incubation time (8 hours).