Simultaneous T Cell Activation and Macrophage Polarization to Promote Potent Tumor Suppression by Iron Oxide‐Embedded Large‐Pore Mesoporous Organosilica Core–Shell Nanospheres

Abstract Nanomaterial‐based immunotherapy stimulating T cell activation or tumor‐associated macrophage (TAM) conversion holds great promise for promoting tumor suppression. Herein, a novel nanoplatform, iron oxide‐embedded large‐pore mesoporous organosilica nanospheres (IO‐LPMONs), is prepared for the first time to simultaneously activate cytotoxic T cells and polarize macrophages for potent tumor immunotherapy. The IO‐LPMONs have large mesopores (6.3 nm) and inorganic–organic hybrid shells, which contribute to a high payload (500 µg mg−1) of the antigen ovalbumin (OVA). The IO‐LPMONs effectively deliver OVA to dendritic cells (DCs) and activate DCs. Subsequently, high activation of both CD4+ and CD8+ effector antigen‐specific T cells is achieved for powerful antitumor effects. Moreover, the IO‐LPMONs also act as an immune modulator to polarize TAMs from an immunosuppressive M2 to a tumor‐killing M1 phenotype, which induces efficient apoptosis of tumor cells. The combined T cell activation and macrophage polarization strategy based on the IO‐LPMONs elicits remarkable combined antitumor effects in vivo, showing great promise for tumor treatment.