Enhanced Cancer Immunotherapy by Bacterial Cytoplasmic Membranes Coated Nanovaccines for Co-Delivery of Ovalbumin Antigen and Immune Adjuvants to Dendritic Cells in Lymph Nodes.

INTRODUCTION: Tumor vaccines can activate tumor-specific immune responses to inhibit tumor growth, recurrence, and metastasis. However, the efficiency of antigen and adjuvants combined delivery to lymph nodes (LNs) is relatively low, leading to weak immune stimulation and tolerance. In this study, a tumor nanovaccine was constructed for the targeted dendritic cells (DCs)-mediated immunotherapy.

METHODS: Ovalbumin (OVA) antigen was first loaded into manganese-doped mesoporous silica nanoparticles (MMSNs) and coated with bacterial cytoplasmic membrane (BM), which was further inserted with mannose to prepare OVA@MMSNs@BM-Man nanovaccines. In vitro and in vivo experiments were conducted to assess their properties and function of the synthesized nanovaccines.

RESULTS: The nanovaccine can effectively target DCs in LNs by the combination of mannose with mannose receptor (CD205). BM serves as an immune adjuvant and co-delivers with OVA antigen, effectively improving antigen presentation efficiency. In an acidic environment, the Mn2+ produced by the degradation of MMSNs can not only serve as an MR imaging agent but also activate the cGAS-STING pathway, followed by the release of IFN-β. The activated DCs further activate the body's cytotoxic T cells (CTLs), thereby exerting anti-tumor effects.

THE CONCLUSION: This study will provide a new idea for the construction of tumor nanovaccines.