Lymph node-targeted delivery of Lonicera japonica thunb. polysaccharides for enhancing antitumor immunotherapy

Abstract

Dendritic cells (DCs) are crucial for the initiation and regulation of innate and adaptive immunity. Their maturity and infiltration in the tumor largely determine the efficiency of antigen presentation, the CTL responses, and the prognosis of tumors. However, the application of common immunoregulatory plant polysaccharides to DCs in vivo still represents major challenges due to the off-target effect and short biological lifespan. Lonicera japonica Thunb. polysaccharides (LJP) were found to exert benign immunoregulatory ability, but the effectiveness of utilizing LJP alone is unsatisfactory. As a result, we innovatively encapsulated LJP in into the exosomes derived from mouse bone mesenchymal stem cells (BMSCs) to form a DC-activated inducer (LJP-exosome). LJP-exosomes possessed a profound ability to target lymph nodes and the co-stimulatory capability of DCs compared with the application of LJP alone. Adequate results have shown that DCs primed by LJP-exosomes enhanced the tumor-reactive CD8⁺ T cell responses, leading to prophylactic tumor inhibition in an immunologically ignorant tumor model. The study proposed offers a promising strategy for enhancing the immune activation efficacy of extracted polysaccharides of traditional Chinese medicine by building the patients’ immunity, thus consolidating the overall prognosis.