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

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.