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Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Photodynamic activities of silicon (IV) phthalocyanines with different charges and their synergistic efficacy with
Yan-Ju Liu1, Qing-Yan Hu1, Hong-Jie Sun1
1College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350108, China.
Photodynamic therapy (PDT) combined with Immune checkpoint blockade (ICB) therapy has made significant achievements in the treatment of advanced metastatic tumors. However, it is still a great challenge to find a simple and effective photosensitizer for matching photodynamic immunotherapy. In this study, we report a treatment approach that combines PDT induced by three silicon (IV) phthalocyanines (SiPcs) with anti-PD-L1 antibody, to induce a systemic anti-tumor immune response and achieve a synergistic anti-tumor effect. Among the SiPcs, neutral SiPc 1 exhibited the highest photodynamic anticancer activity in vitro, while the cationic SiPc 2 showed the highest synergistic anti-tumor effect with ICB in vivo. For SiPc 2, we found that the combined PDT-ICB therapy achieved a tumor inhibition rate of 81% in distant tumors, while single PDT or single ICB had almost no inhibitory effect in the B16-F10 tumor model. After activation of the immune system by the combination of anti-PD-L1 antibody and PDT, we also observed an increase in the infiltration of T cells in the tumor microenvironment. Interestingly, when anti-PD-L1 antibody was used in combination with the positively charged SiPc 2 for PDT, the increase in CD8+ T cells was most significant. These results demonstrate that the structurally defined bis-cationic SiPc 2 is a highly promising photosensitizer, particularly suitable for PDT combined with immunotherapy.
Photodynamic therapy (PDT) combined with Immune checkpoint blockade (ICB) therapy has made significant achievements in the treatment of advanced metastatic tumors. However, it is still a great challenge to find a simple and effective photosensitizer for matching photodynamic immunotherapy. In this study, we report a treatment approach that combines PDT induced by three silicon (IV) phthalocyanines (SiPcs) with anti-PD-L1 antibody, to induce a systemic anti-tumor immune response and achieve a synergistic anti-tumor effect. Among the SiPcs, neutral SiPc 1 exhibited the highest photodynamic anticancer activity in vitro, while the cationic SiPc 2 showed the highest synergistic anti-tumor effect with ICB in vivo. For SiPc 2, we found that the combined PDT-ICB therapy achieved a tumor inhibition rate of 81% in distant tumors, while single PDT or single ICB had almost no inhibitory effect in the B16-F10 tumor model. After activation of the immune system by the combination of anti-PD-L1 antibody and PDT, we also observed an increase in the infiltration of T cells in the tumor microenvironment. Interestingly, when anti-PD-L1 antibody was used in combination with the positively charged SiPc 2 for PDT, the increase in CD8+ T cells was most significant. These results demonstrate that the structurally defined bis-cationic SiPc 2 is a highly promising photosensitizer, particularly suitable for PDT combined with immunotherapy.
