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. A biomimetic nanoemulsion camouflaged with a PD‐1‐expressing cell membrane is fabricated. The PD‐1 protein on the membrane blocks the PD‐L1 on tumor cells to relief the immune brake. The perfluorocarbon inside the nanoemulsion supplement oxygen for PDT in hypoxic tumors. The codelivery of photosensitizer DVDMS and PD‐1 protein realizes effective synergistic photodynamic‐immunotherapy against hypoxic breast tumors.