Silicon-based metal-organic frameworks (SiMOFs) for immunogenic cell death in cancer therapy

Silicon-based nanomaterials, known for their unique properties and favorable biocompatibility, significantly impact sectors like energy, electronics, and biomedicine. Recently, metal-organic frameworks (MOFs) have emerged as promising candidates for biomedicine, characterized by adjustable chemical composition, high porosity, and biodegradability. However, the combination of silicon with MOFs to create silicon-based MOF nanostructures (SiMOFs) remains underexplored. Herein, we establish a diverse library of SiMOFs with various nanostructures, including flower-like, capsule-like, hexagonal snowflake-like, and necklace-like morphologies via microwave-assisted synthesis. These SiMOFs, with their spacious interiors, are ideal for drug delivery. They are used to load drugs and create drug-loaded SiMOFs (e.g., SiFeO). SiFeO exhibits excellent photothermal effects and high reactive oxygen species (ROS) generation capacity, enabling synergistic treatments involving chemo-chemodynamic-photothermal therapy. This approach efficiently triggers immunogenic cell death (ICD) and demonstrates excellent antitumor efficacy in vivo. Immunofluorescence staining reveals that the synergistic therapy can modulate the tumor microenvironment (TME) by reducing M2-phenotype macrophages, increasing the activation of antigen-presenting cells (APCs), enhancing the infiltration of CD4⁺ and CD8⁺ T cells, elevating Granzyme B production, and decreasing the presence of immunosuppressive regulatory T cells (Tregs). Consequently, drug-loaded SiMOFs-mediated combination therapy effectively reverses the immunosuppressive TME and activates robust antitumor immune responses by inducing ICD in tumor cells, ultimately achieving superior anticancer efficacy.