The synthesis, photophysical and biological properties of 5,10,15,20-tetra(4-substituted phenyl)tetrabenzoporphyrin derivatives

Photodynamic therapy (PDT) had garnered considerable focus owing to its high photoactivation efficacy and low systemic toxicity. The performance of PDT heavily relied on the behavior of photosensitizers. In this study, a series of new 5,10,15,20-tetra(4-substituted phenyl)tetrabenzoporphyrin derivatives were prepared and their antitumor effects in vitro and in vivo were evaluated. These new compounds presented an absorption peak at ∼700 nm within the phototherapeutic window (600–760 nm). Their effective ROS generation capacities were predominantly verified via the type II mechanism during the irradiation process. In vitro experiments displayed that all compounds exhibited notable phototoxicity with low dark toxicity (IC₅₀ > 76 μM) toward Eca-109 cells. Among them, VI showed obvious photoactivation with a cell survival rate reduction to 7 % at a concentration of 10 μM after exposure to 650 nm laser light (12 J/cm²). In vivo studies revealed that VI had significant antitumor effects with inhibition rate up to 94 %. Subcellular experiments demonstrated that VI distributed mainly in mitochondria, lysosomes and partially in endoplasmic reticulum. Thus, compound VI, which possessed long-wavelength and multi-wavelength absorption capabilities, high photocytotoxicity and low dark toxicity to tumor, would emerge as a promising photosensitizer for individual photo-diagnosis and photodynamic therapy.