Phthalocyanine-based photosensitizers combined with anti-PD-L1 for highly efficient photodynamic immunotherapy

Immune checkpoint blockade (ICB) therapy combined with Photodynamic therapy (PDT) has shown great potential in the treatment of advanced metastatic tumors. However, it is still an important challenge to find a simple and effective photosensitizer for matching photodynamic immunotherapy. In this paper, we report a treatment method that combines PDT caused by three zinc(II) phthalocyanines (ZnPcs) with a different charge, and a checkpoint inhibition agent, namely anti-PD-L1 antibody, to induce systemic antitumor immunity. Among the ZnPcs, the neutral ZnPc 1 showed the highest photodynamic activity, while the cationic compound 2 exhibited the highest synergistic antitumor effect with ICB. For ZnPc 2, the tumor inhibition rate of PDT-ICB combined therapy for distant tumors was found to be as high as 89%, but PDT alone or ICB alone could hardly cause an inhibitory effect in a B16–F10 tumor model. We also detected an increase in T cell infiltration in the tumor microenvironment after the immune system was activated by a combination of anti-PD-L1 antibody and PDT. It was interesting to find that CD8+ T cells increased most significantly for the combination of anti-PD-L1 antibody and PDT by the positively charged compound 2. Moreover, the combination of ZnPc 2-PDT and ICB could efficiently inhibit the recurrence of tumors. The results suggest that the mono-cationic ZnPc 2 with a well-defined structure and ease of preparation, is a highly promising photosensitizer specifically for PDT combined with immunotherapy.