Targeted immune activation via mannose-decorated erythrocyte membrane PLGA nanoparticles: Sustained delivery of chuanminshen polysaccharides boosts adaptive immunity

The clinical application of Chuanminshen violaceum polysaccharides (CVP), a natural immunomodulator with intrinsic antioxidant activity, is constrained by rapid systemic clearance, limited tissue specificity, and short-lived bioactivity. To address these limitations, a multifunctional biomimetic nanoplatform incorporating erythrocyte membrane camouflage, mannose-mediated active targeting, and squalene-stabilized Pickering emulsion technology was developed. CVP-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CVPP) were fabricated via solvent evaporation, coated with erythrocyte membranes, and subsequently functionalized with mannose to obtain CVPP@M-M. This dual modification enabled selective recognition by macrophage and dendritic cell (DC) mannose receptors, while the erythrocyte membrane imparted prolonged systemic circulation. Subsequent emulsification for the first time with squalene yielded CVPP@M-M-PPAS, a Pickering emulsion designed for enhanced lymph node delivery. In vitro, CVPP@M-M-PPAS significantly promoted macrophage activation, as evidenced by elevated CD80⁺/CD86⁺ expression, compared with free CVP. In vivo, intramuscular co-administration with ovalbumin (OVA) antigen induced pronounced DC maturation and T cell polarization in the spleen. This formulation also elicited robust and sustained production of antigen-specific IgG, accompanied by increased upregulation of pro-inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ). In vivo imaging demonstrated prolonged lymph node retention (> 336 h) with a near-linear fluorescence decay profile, confirming controlled release kinetics. By integrating stealth properties, receptor-specific targeting, and emulsion-enabled lymphatic trafficking, this nanoplatform effectively circumvents the pharmacokinetic and biodistributional barriers of plant-derived polysaccharides, enabling durable humoral and cellular immune responses. This strategy offers a generalizable framework for translating natural immunomodulators into clinically viable nanotherapeutics.