Relighting Photosensitizers by Synergistic Integration of Albumin and Perfluorocarbon for Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) is hampered by poor water solubility and skin phototoxicity of photosensitizers (PSs). Incorporation of PSs into nanocarrier (Nano-PDT) has been designed to overcome these problems. However, self-quenching of PSs highly condensed in Nano-PDT significantly reduced singlet oxygen ( 1 O 2 ) generation, resulting in unsatisfactory PDT efficacy. Here, we developed a novel tripleffect Nano-PDT, which has a special core–shell nanostructure by synergistic integration of perfluorotributylamine (PFTBA) and human serum albumin (HSA) to improve PDT. It has three mechanisms to relight quenched PSs, thereby generating more 1 O 2 . First, PSs uniformly dispersed in the shell, preventing self-quenching caused by π–π stacking. Second, HSA as nanocarrier extends the triplet-state lifetimes of PSs, increasing the amount of 1 O 2 . Third, PFTBA as core dissolves and protects 1 O 2 to extend the duration time of action of 1 O 2 . Compared with PS-encapsulated Nano-PDT, the self-quenching of PSs in tripleffect Nano-PDT can be effectively overcome. The fluorescence and 1 O 2 generation of PS are increased by approximately 100-fold and 15-fold, respectively. After intravenous injection into tumor-bearing mice, the tumor growth is significantly inhibited, while the PS-encapsulated Nano-PDT has almost no effect. The novel tripleffect Nano-PDT may guide improvement of existing clinical PDT and future PDT design.