Figure 6:

Overview of the proposed mechanism of action of PAI nanovaccines based on mechanistic analyses herein. PAI nanovaccines enhance endocytosis by antigen-presenting cells on account of their ~50 nm structure. Their secondary structure localizes effects to the injection site. Upon endocytosis, they then activate endosomal TLR7 and induce lysosomal rupture to result in NLRP3 inflammasome activation and cytosolic delivery of neoantigen to afford enhanced antigen presentation on MHC-I. When nanovaccines are injected peritumorally, they induce tumor localized, neoantigen-specific CD8⁺ T cell responses characterized by secretion of IFN-γ and GNZB to afford tumor clearance. Created using Biorender.com.