Bioengineering a needle-free intranasal nanovaccine with TLR7/8 agonist for potent antimetastatic immunity

Recent outbreaks and the global spread of infectious diseases have underscored the need for mucosal vaccines capable of inducing both antigen-specific humoral and cellular immunity. Because conventional systemic vaccination often elicits limited immune responses at mucosal surfaces, needle-free mucosal vaccination represents an attractive strategy for disease prevention and mass immunization. However, rapid antigen degradation and clearance at mucosal sites remain major barriers. Here, we developed a cationic polymeric nanoparticle platform (DA3) that co-delivers anionic ovalbumin (OVA) and the TLR7/8 agonist resiquimod (R848) to improve antigen stability and immunogenicity. The DA3/R848/OVA nanovaccine enhanced dendritic cell activation and, in a B16-OVA melanoma model, inhibited tumor growth, prolonged survival, and induced immunological memory following intranasal administration. These findings demonstrate the potential of DA3 as a needle-free mucosal nanovaccine platform.