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.

Keywords: T cell activation; cancer immunotherapy; iron oxide; macrophage polarization; mesoporous organosilica.