Effects of Skeleton Structure of Mesoporous Silica Nanoadjuvants on Cancer Immunotherapy

Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure -Si-O-Si- framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application. Three commonly used mesoporous silica nanoparticles (MSNs) with different skeletons are synthesized by using different silica sources, such as TEOS for MSN, TEOS/BTEE for EMSN, and TEOS/BTES for TMSN. Compared with other two OMSNs, the OTMSN effectively targeted lymph nodes, activated DCs maturation, stimulated the proliferation of CD4+, CD8+ T cells, and polarized M2 phenotype macrophages into M1 phenotype macrophages, and reversed immunosuppressive tumor microenvironment.image