Mannose modified soy peptide aggregates as a delivery system for vitexin: Enhancing stability and macrophage-targeted anti-inflammatory efficacy.

Soy peptide aggregates (SPA) are the hydrolysate products of soy protein isolate, which possess good biocompatibility and self-assembly properties, making them excellent materials for nanocarriers. In this study, a green, food-grade nanocarrier based on mannose-modified soy peptide aggregates (M-SPAV) was developed for the efficient encapsulation and targeted delivery of vitexin, a bioactive polyphenol, which has poor water solubility and low bioavailability. The mannose modification of the soy peptide aggregates was performed via a mild and feasible glycosylation method to achieve macrophage targeting. The results demonstrated that nanoparticles prepared at a mannose-to-soy protein aggregate mass ratio of 1:1 exhibited a minimum particle size of 142 nm and achieved an encapsulation efficiency as high as 93.46%. Notably, M-SPAV displayed excellent stability across a broad pH range (3.0-8.0), under high ionic strength conditions and prolonged storage, while effectively protecting vitexin and maintaining antioxidant capacity throughout simulated gastrointestinal digestion. Furthermore, mannose modification not only improved the physicochemical properties of the soy protein aggregates but also endowed the nanoparticles with specific macrophage-targeting capability through receptor recognition. This nanoparticle system substantially enhanced the cellular uptake efficiency of vitexin. Consequently, M-SPAV significantly reduced intracellular reactive oxygen species (ROS) levels in LPS-stimulated macrophages compared to free vitexin, and anti-inflammatory activity by inhibiting the TLR4 / MyD88 / NF-κB signaling axis and regulating macrophage polarization. In summary, M-SPAV provides a promising food-grade nanoplatform for precision immunomodulatory intervention in macrophage-associated inflammatory diseases.