A universal silica nanosphere platform for in situ nano-encapsulation: Toward imaging-guided synergistic tumor therapy and immune modulation.

This study developed an in situ encapsulation strategy based on mesoporous silica, successfully constructing a nano-co-delivery system (CA@SiO2) for multiple quantum dots (e.g., Ag2S, AgInS2, ZnAgInS) and the natural antitumor compound celastrol (Cel). Comprehensive characterization confirmed the uniform distribution of quantum dots (QDs) within the mesopores, their well-preserved crystallinity, and effective retention of fluorescence properties. In vitro studies demonstrated that CA@SiO2 could respond to the weakly acidic and high glutathione (GSH) tumor microenvironment (TME), leading to the co-release of Cel and Ag2S. This process depleted intracellular GSH, elevated reactive oxygen species (ROS) levels, induced mitochondrial damage and immunogenic cell death (ICD), thereby significantly inhibiting tumor cell proliferation and promoting apoptosis. In a CT26 tumor-bearing mouse model, CA@SiO2 exhibited excellent tumor-targeting capability and potent tumor growth inhibition (tumor growth inhibition rate of 83.6%), along with a marked extension of mouse survival. Mechanistically, this system remodeled the immune-suppressive TME by promoting dendritic cell maturation, enhancing CD4+/CD8+ T-cell infiltration, reducing regulatory T cells and myeloid-derived suppressor cells, and upregulating pro-inflammatory cytokine expression. Furthermore, biosafety evaluations confirmed its favorable hemocompatibility and in vivo organ safety. This work provides a novel strategy and experimental evidence for the synergistic application of inorganic nanomaterials and natural products in tumor therapy and immune modulation.