Lycium barbarum polysaccharides (LBPs) are recognized as key bioactive constituents of Lycium barbarum with diverse biological activities. However, current research on LBPs is largely confined to crude extracts, offering limited insight into the structural properties underlying their biological effects. In this study, we separated crude LBP into acidic LBP (ALBP) and neutral LBP (NLBP), which exhibited distinct physicochemical properties. ALBP, consisting of 76.18 % galacturonic acid (GalA), demonstrated crystallinity, thermal stability and gelatinous characteristics. In contrast, NLBP, with only 3.16 % GalA, displayed a more porous structure and superior fluidity. Furthermore, functional analysis revealed that NLBP exhibited enhanced immunoregulatory effects by activating dendritic cells and repolarizing macrophages. In a B16F10 melanoma-bearing C57BL/6 J mice model, NLBP significantly inhibited tumor growth with an inhibition rate of 66.7 % through macrophage repolarization. The findings highlight the distinct biological effects of NLBP and ALBP, providing a theoretical foundation for the refined utilization of LBP.

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-Araf-(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.

Curcumin is a natural bioactive compound with a wide range of established health benefits. However, its practical applications are severely limited due to extremely poor aqueous solubility, which directly leads to low bioavailability. While polysaccharides like Lycium barbarum polysaccharide (LBP) can partially improve curcumin solubility, their solubilization efficiency remains limited. To overcome this challenge, we implemented ultrasonication as an effective processing strategy to enhance LBP's capacity to promote curcumin dissolution. Our findings show that ultrasound-induced cavitation and related physico-chemical effects markedly improve LBP's solubilization performance. The ultrasonically-assisted curcumin-LBP complex (CL-U) was systematically optimized through response surface methodology (RSM), identifying ultrasonic power, duration, and temperature as critical parameters. Extensive characterization verified that ultrasonication is essential for producing spherical core-shell nanoparticles, achieving a 2.23-fold enhancement in drug loading efficiency along with superior colloidal stability. Additional evidence from FTIR spectroscopy and acid hydrolysis experiments confirmed that ultrasonication reinforces hydrogen bonding as the principal intermolecular interaction stabilizing the complex. Biologically, CL-U demonstrated rapid cellular uptake in 4T1 cells within one hour and showed substantially improved antioxidant performance in both DPPH and ABTS assays. These functional gains are directly linked to the ultrasound-mediated improvements in solubility, stability, and bioavailability. This research establishes ultrasonication as a crucial sonochemical approach for constructing advanced polysaccharide-based delivery systems, providing a viable pathway for curcumin utilization in functional foods and pharmaceutical products.