Mannose receptor targeted PLGA nanoparticles ofEucommia ulmoidespolysaccharide through the MAPK and NF-κB pathway to enhance the immune activity of BMDCs.

Mannosylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating Eucommia ulmoides polysaccharides (EOPP) were developed as a targeted immunomodulatory delivery system. In vitro evaluations confirmed that EOPP exhibited low cytotoxicity toward spleen lymphocytes while significantly increasing their proliferation and cytokine secretion (IL-6 and IFN-γ). When co-delivered with ovalbumin (MN-EOPP/OVA), the system further enhanced the secretion of TNF-α, IL-12, IL-6, and IFN-γ by immune cells and induced cytoskeletal remodeling and maturation in bone marrow-derived dendritic cells (BMDCs). Transcriptomic profiling revealed significant upregulation of immune-related genes, with KEGG and PPI analyses identifying activation of key signaling pathways, including MAPK (ERK, p38, JNK) and NF-κB. These pathways drive the expression of genes involved in antigen processing and dendritic cell function. Overall, MN-EOPP/OVA effectively enhanced both humoral and cellular immune responses by synergistic delivery of antigen and immunopotentiator, supporting its potential as a next-generation vaccine adjuvant strategy.