A structurally distinct arabinose-bridged arabinogalactan from Lycium barbarum as a TLR4-activating adjuvant for nanovaccine-based cancer immunotherapy

Current studies on plant-derived adjuvants focus on heterogeneous or partially characterized polysaccharides, while the adjuvanticity of structurally defined, arabinogalactan (AG)-rich polysaccharide in cancer nanovaccine settings remains unexplored. Here, we identify and characterize NLBPE1, a homogeneous AG-rich polysaccharide isolated from Lycium barbarum , which features an atypical arabinose-bridged structure. Unlike canonical AG-I or AG-II motifs, NLBPE1 contains galactose side chains connected to the rhamnogalacturonan backbone via  → 5)- α -Ara f -(1 → linkages, forming a structurally distinct AG topology. Mechanistic studies demonstrate that NLBPE1 activates dendritic cells through the TLR4–IKK–NF-κB signaling axis, promoting antigen uptake, cross-presentation, and proinflammatory cytokine release. When co-formulated in a PLGA-based nanovaccine with a model antigen, NLBPE1 markedly enhances CD8 + T cell priming, leading to effective tumor control in vivo . Moreover, combination with anti-PD-1 immune checkpoint blockade yields synergistic antitumor responses in a melanoma model. Together, these findings establish NLBPE1 as a structurally and mechanistically distinct polysaccharide adjuvant with translational potential for next-generation cancer nanovaccine strategies.