Extra-Large Pore Mesoporous Silica Nanoparticles Enabling Co-Delivery of High Amounts of Protein Antigen and Toll-like Receptor 9 Agonist for Enhanced Cancer Vaccine Efficacy.

Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes. Extra-large pores of approximately 25 nm and additional surface modification of XL-MSNs resulted in significantly higher loading of antigen protein and toll-like receptor 9 (TLR9) agonist compared with conventional small-pore MSNs. study showed the enhanced activation and antigen presentation of DCs and increased secretion of proinflammatory cytokines. study demonstrated efficient targeting of XL-MSNs co-delivering antigen and TLR9 agonist to draining lymph nodes, induction of antigen-specific cytotoxic T lymphocytes (CTLs), and suppression of tumor growth after vaccination. Furthermore, significant prevention of tumor growth after tumor rechallenge of the vaccinated tumor-free mice resulted, which was supported by a high level of memory T cells. These findings suggest that mesoporous silica nanoparticles with extra-large pores can be used as an attractive platform for cancer vaccines.