Polyethylenimine-coated PLGA nanoparticles containing Angelica sinensis polysaccharide promote dendritic cells activation and associated molecular mechanisms

Abstract

Cationic PLGA nanoparticles-based delivery systems have been extensively employed as nanocarriers for drugs and antigens in recent years. Herein, we investigated the effects of polyethylenimine-coated PLGA nanoparticles containing Angelica sinensis polysaccharide (ASP) system (ASP-PLGA-PEI) on dendritic cells (DCs) activation and maturation, and further explored the changes of transcriptome and underlying mechanism of DCs activation based on RNA-seq. Our results demonstrated that ASP-PLGA-PEI obviously promoted the activation and maturation of DCs. Meanwhile, RNA-seq analysis results exhibited 2812 differentially expressed genes (DEGs) between ASP-PLGA-PEI and control group, and the DCs activation by ASP-PLGA-PEI stimulation mainly related to phagosome, antigen processing and presentation, proteasome, lysosome, protein processing in endoplasmic reticulum and other pathways by KEGG pathways analysis. Furthermore, ASP-PLGA-PEI nanoparticles increased the levels of pJAK2 protein, and the expression of co-stimulatory molecules and cytokines induced by ASP-PLGA-PEI nanoparticles were decreased with the presence of the inhibitor of JAK2/STAT3 signaling pathway. In addition, the nanoparticles were internalized by DCs mainly through the clathrin-mediated endocytosis and micropinocytosis. These results suggested that the DCs activation and maturation stimulated by ASP-PLGA-PEI were regulated via a complex interaction network, in which the JAK2/STAT3 signaling pathway played a crucial role.

Keywords: Angelica sinensis polysaccharide; Cationic PLGA nanoparticles; Dendritic cells; Molecular mechanisms; RNA-seq.