Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph₄TBP) derivatives were designed, prepared, and characterized. All m-Ph₄TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph₄TBPs demonstrated high photoactivity, among which compounds I₄, I₆, I₁₂, and I₁₃ induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I₄ and I₆-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph₄TBPs, glycol m-Ph₄TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph₄TBP I₁₂ displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.