Lysosome-targeted 5,15-diaryltetraacenaphthoporphyrin as a promising immunoinducer for enhanced photodynamic therapy in melanoma

Photodynamic therapy (PDT) has become an important tumor treatment. At present, the photosensitizers (PSs) with porphyrin structure have attracted extensive attention due to their stable chemical structure and effective photodynamic effect. However, most of these PSs have short absorption wavelength and low singlet oxygen (¹O₂) generation rate, which seriously affects the efficacy of photodynamic therapy. A series of novel 5,15-diaryltetraacenaphthoporphyrin PSs were synthesized and their photodynamic activities were evaluated, whose absorption wavelength was visibly redshifted and ¹O₂ generation rate was significantly increased due to the inclusion of acenaphthene at the β site of porphyrin. The experimental results show that the PDT process based on compound P4 can not only directly kill tumor cells through the generated Reactive Oxygen Species, but also induce immunogenic cell death to produce anti-tumor immune effects. In addition, in vivo studies have also shown that P4-based PDT can effectively inhibit tumor growth. Therefore, P4 has the potential to become a photosensitive immunoinducer.

Immunogenic cell death; Melanoma; Photodynamic therapy; Singlet oxygen; Tetraacenaphthoporphyrin.