Dual-targeting pluripotential biomimetic nanovehicle modulates tumor immune microenvironment for potentiated cancer chemoimmunotherapy

Chemoimmunotherapy holds promise in enhancing tumor immunogenicity via inducing immunogenic cell death (ICD), while still fails to elicit robust anti-tumor immunity mainly due to the low drug delivery efficiency and the immunosuppression in tumor microenvironment (TME). Herein, an engineered pluripotential biomimetic nanovehicle favorable for tumor-targeted drug delivery and TME modulation is developed by simply incorporating tumor cell membrane into a carbonic anhydrase IX inhibitor (CAI) chemically-modified liposome. Profiting from plasma membrane-mediated homotypic adhesion and CAI-mediated active targeting, ADM exhibits high affinity for autologous tumors and can improve the accumulation of drugs into the tumor tissues. Importantly, ADM can metabolically inhibit extracellular H + production to remodel the acidic immunosuppressive TME and serve as a tumor antigen pool, potentiating anti-tumor immune response. As a result, ADM facilitates tumor-targeted delivery of doxorubicin (DOX), and synergizes DOX-mediated ICD induction with a synergistic TME modulating feat, thus reinforcing cancer chemoimmunotherapy. The rationally designed pluripotent biomimetic nanovehicle orchestrates precision drug delivery with simultaneous immunomodulation, furnishing a compendious yet powerful platform for augmenting anti-tumor immunity.