Abstract
Porphyrins, as photosensitizers for photodynamic therapy, is used to treat various cancers. In this study, three different side-chain variants of thiophene-zinc porphyrins were synthesized (Zn-P1, Zn-P2, and Zn-P3). Among the synthesized compounds, Zn-P1 exhibited the highest activity and demonstrated superior singlet oxygen generation capability according to both density functional theory calculations and singlet oxygen generation experiments. Our cytotoxicity assays revealed that Zn-P1 exhibited remarkable phototoxicity along with a pronounced selectivity for HepG2 cells. This selectivity was confirmed by cell staining experiments, which showed obvious apoptotic processes. Further insight into this anticancer mechanism was provided by cell reactive oxygen species experiments, which explained the induction of cancer cell apoptosis. Light-activated production of reactive oxygen species by photosensitizers initiates the apoptotic cascade in cancer cells. This study highlights the utility of cationic porphyrin photosensitizer complexes in photodynamic therapy and provides new insights for the development of innovative photosensitizers in cancer treatment.
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