Genetically engineered eukaryocyte-bacteria hybrid membrane-camouflaged nanoemulsion for three-pronged synergistic cancer therapy

Despite the tremendous clinical benefits of immune checkpoint blockade (ICB), it still suffers from several drawbacks such as low response rate, off-target toxicity, and high costs. To address these issues, herein, a hybrid membrane (PSHM) consisting of outer membrane vesicles of attenuated Salmonella typhimurium (SM) and the membrane of PD-1-expressing HEK293T cells (PM) is fabricated to coat nanoemulsion for three-pronged synergistic photothermal-immunotherapy. First, SM upregulates the PD-L1 expression of tumor cells to enhance the response rate of PD-L1 blockade. Second, SM targets the nanoemulsion to the hypoxic tumor to realize targeted PD-L1 blockade mediated by PD-1 proteins on the PM. Third, SM induces erythrocyte extravasation into tumors for photothermal ablation of tumors without damaging surrounding tissues and thereby enhancing anticancer immunity. The hybrid membrane-coated nanoemulsion arouses a potent antitumor T-cell immunity and inhibits tumor growth and metastasis. Therefore, this study presents a promising hybrid membrane coating strategy to potentiate ICB.