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 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 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 IL-6 and 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.