Lipid Coating of Mesoporous Silica Nanoparticles Leads to Efficient Antigen Delivery to Lymph Nodes for Cancer Vaccination.

The enrichment of antigens in lymph nodes and the ensuing antigen presentation constitute crucial steps in determining the efficacy of tumor vaccines. However, antigen delivery is restricted by enzyme degradation, immune system clearance, and the difficulty of crossing biological barriers. In this study, mesoporous silica nanoparticles (MSNPs) were prepared for antigen loading and were further coated with a phospholipid bilayer membrane (named silicasomes) to improve the delivery efficiency to lymph nodes. Our results showed that silicasomes exhibited superior lymph node enrichment compared to the bare MSNPs following subcutaneous injection. Moreover, their efficacy as a tumor vaccine was validated in the B16-OVA tumor model by loading the ovalbumin antigens (OVA257-264). Besides, the toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA), a component of bacterial lipopolysaccharides, was incorporated into the phospholipid membrane on the surface of silicasomes as an adjuvant. The silicasome-OVA257-264 with the addition of MPLA exhibited a more potent antitumor effect, triggering the infiltration of specific T cells into the tumor. These results demonstrated that lipid coating on MSNPs significantly enhanced their delivery efficiency to lymph nodes and enabled synergistic immune activation of tumor antigens and adjuvants, highlighting their potential as effective vehicles for cancer immunotherapy.