Biomimetic Nanoemulsion for Synergistic Photodynamic-Immunotherapy Against Hypoxic Breast Tumor.

Photodynamic therapy (PDT) is commonly used as an "in situ vaccine" to enhance the response rate of PD-1/PD-L1 antibodies. Unfortunately, the high cost and adverse effects of these antibodies, and the hypoxic state of solid tumors limits the efficacy of synergistic photodynamic-immunotherapy. Here, we developed a biomimetic nanoemulsion camouflaged with a PD-1-expressing cell membrane for synergistic photodynamic-immunotherapy against hypoxic breast tumors. The perfluorocarbon of the nanoemulsion could provide oxygen as the source of PDT against hypoxic tumors. Moreover, co-delivering a photosensitizer and the PD-1 protein (substituting for a PD-L1 antibody) achieves the synergy effect of PDT and immunotherapy. Synergistic photodynamic-immunotherapy completely inhibited primary and distant subcutaneous 4T1 tumors, mechanistically by boosting the maturation of dendritic cells and tumor infiltration of cytotoxic T lymphocytes.