Microalgae-Derived Microparticles Improve Immunomodulation via Combined Glycolysis and MAPK Activation

Natural polysaccharides possess potent immunostimulatory properties, but their poor solubility impedes efficiency of cellular delivery. This study focuses on extraction of microparticles (MPs) from<i>Euglena gracilis</i>, a microalgae species characterized by abundant intracellular β-1,3-glucan and flexible cell membrane. We introduce an<i>E. gracilis</i>-derived MP (MP_EG) system as a natural carrier for solubilized β-glucan. The MP_EG system enhances β-glucan's solubility and loading efficiency through sequential sonication and cell extrusion. <i>In vitro</i> studies reveal that MP_EG utilizes multiple endocytosis pathways, including phagocytosis, clathrin-mediated, and lipid raft-mediated routes, for effective β-glucan delivery into cells. Upon cellular internalization, MP_EG components trigger dual activation of the MAPK signaling pathway and glycolysis in macrophages, leading to enhanced production of pro-inflammatory cytokines and lactic acid, ultimately strengthening innate immune responses. This MP_EG system offers a promising approach to harnessing the immunostimulatory properties of natural polysaccharides while overcoming their solubility limitations, opening new avenues for targeted cellular delivery in immunomodulation therapies.