Porphyrin derivatives are the first-generation photosensitizers, and to design a strong near-infrared (NIR)-absorbing porphyrin with good water solubility is highly desired for better therapeutic effect to treat tumors. Herein, three new porphyrin derivatives, 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (P1), 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) zinc porphyrin (ZnP1), and 5,15-bis(3,4-dimethoxyphenyl)-10,20-bis((4-methoxyphenyl)ethynyl) zinc porphyrin (ZnP2) have been synthesized. Among them, ZnP2 shows the longest and most intensive Q-bands in the near-infrared (NIR) region, as it endows the strongest light-harvesting capability and deepest tumor tissue penetration. The three porphyrin derivatives were prepared into nanoparticles (NPs) via nanoprecipitation method, and the NPs exhibit good water dispersibility and passive tumor-targeting property through enhanced permeability and retention effect. Furthermore, these NPs demonstrate both photodynamic and photothermal effects. Through a systematic study of the singlet oxygen quantum yield and cytotoxicity of P1, ZnP1, and ZnP2 NPs in vitro on Hela cells, it is found that ZnP2 shows the highest singlet oxygen quantum yield (79%), and its NPs show the best therapeutic efficacy in vitro. In vivo experiments disclosed that ZnP2 NPs present high phototoxicity, low dark toxicity, and excellent biocompatibility, and could be used as promising photothermogenic photosensitizer for cancer treatment.
Keywords: NIR absorption; photodynamic therapy; photosensitizer; photothermal therapy; porphyrin.