Self-Assembled Two-Dimensional Chiral Meso-Topography Determines the Balance of Cellular and Humoral Immunity Against...

The development of nanomaterials-based cancer vaccines has broadened the scope of immunotherapy. Nanomaterials with characteristics such as chirality, 2D, and flexibility have attracted widespread attention because they can maximize the interface between the materials and immune cells. Here, we report the fabrication of 2-D mesoporous silica nanodisks with a chiral meso-topography as vaccine adjuvants. These uniform nanodisks, with diameters from 200 nm to 1 µm, possess unique spiral mesoporous patterns of ∼ 10 nm. The thickness of the chiral mesoporous nanodisks can be precisely controlled in units of one layer (∼ 7 nm), thereby achieving precise regulation in surface topology, dimension and flexibility. The unique 2-D chiral mesoporous structure originates from the maximum occupancy of confined space of micellar helical arrangement, which is distinct from conventional methods based on internal tension. The combination of flexibility, 2-D structure and chirality enhances nanodisks' interaction with dendritic cells (DCs), significantly improving DC maturation via Toll-like receptors/Nuclear Factor-kappa B (TLR/NF-κB), Mitogen-Activated Protein Kinase (MAPK) and Focal Adhesion Kinase (FAK) signaling pathways. Upon nanovaccines' activation of DCs in vivo, DCs further presents antigen for activating T cells to trigger balanced cellular and humoral immunity. Subcutaneous injection of the nanodisks-adjuvanted cancer vaccine can significantly inhibit the tumor growth and extend the survival of melanoma-bearing mice to more than 60 days, about three times higher than that of the PBS-treated group. When combined with PD-1 antibody, the cancer vaccines maximize tumor suppression, achieving a tumor-free outcome in one-third of the cases.