Pairing tumor cell vesicle antigens with cationic nano-adjuvants by electrostatic adherence for personalized cancer vaccine

Abstract

Simultaneous co-delivery of both antigens and adjuvants is crucial for the efficient activation of dendritic cells (DCs), but it has often been overlooked in the context of tumor cell-based vaccines. Building on the significant advancements in cationic nano-adjuvants, we proposed a straightforward and effective strategy for crafting personalized cancer vaccines, in which tumor cell vesicle antigens were paired with cationic nano-adjuvants to form nano-network through electrostatic adherence. Our pioneering research indicates that densely arranged nanoparticles can be simultaneously taken up by DCs, thus facilitating the co-delivery of adjuvants and antigens. To further enhance the interaction between DCs and antigens, the antigens-adjuvants nano-network was reconstructed using high aspect ratio silicon dioxide (SiO₂) rods to generate 3D structures with ample interparticle spaces. This fosters a conducive environment for DCs infiltration, thereby optimizing the spatial and temporal orchestration of antigen cross-presentation. When combined with programmed death ligand 1 (PD-L1) immune checkpoint inhibitors, the dual-scale cancer vaccine effectively inhibits tumor proliferation through T cell-mediated mechanisms, resulting in a survival rate of 60 % in mice for over 40 days. In summary, our study introduces an innovative approach to the spatiotemporal orchestration of antigen cross-presentation, providing fresh insights into the construction of cancer vaccines based on tumor cells.