Triply pH-activatable porphyrin as a candidate photosensitizer for near-infrared photodynamic therapy and diagnosis

To achieve highly selective tumor therapy and diagnosis, we have developed a novel low-pH-activatable photosensitizer, AI(4)P, which is a porphyrin derivative possessing four 5-diethylaminoindole units. These 5-diethylaminoindole units enhance internal conversion from the first excited singlet state to suppress fluorescence and photosensitization of singlet oxygen. Upon decreasing pH, AI(4)P becomes protonated form. This protonated form exhibited strong absorption at 740 nm, which is the optimal wavelength for light penetration through living tissues. In addition, the pmtonated form exhibited efficient fluorescence and photosensitization. Therefore, AI(4)P is proposed as a triply activatable near-infrared photosensitizer that can activate near-infrared absorption, fluorescence, and photosensitization simultaneously. The activation ratio was over 200, which represents almost complete activation.