Selenized Polysaccharides Exert Immunotherapy Enhancement by Reprogramming Macrophage Polarization: A Comparative Study of Selenium Forms

Macrophage repolarization from M2 to M1 is a promising strategy for immunomodulatory functional foods. Here, Artemisia sphaerocephala polysaccharide was structurally characterized, and selenized ASPs with controllable selenium (Se) contents and molecular masses were prepared using a dissolution-enhanced magnetic solid acid-catalyzed strategy. Compared with Na 2 SeO 3 and selenium nanoparticles (SeNPs) under Se-equivalent conditions, high-Se SeASP H more effectively promoted M1-like macrophage polarization, as shown by increased CD86, decreased CD206, enhanced proinflammatory cytokine production, and MAPK/NF-κB activation. Conditioned medium from SeASP-reprogrammed macrophages inhibited B16 melanoma cell migration and induced mitochondrial apoptosis through regulation of CXCL12 and apoptosis-related proteins. In B16 melanoma-bearing mice, SeASP H suppressed tumor growth, increased F4/80 + CD86 + signals, reduced F4/80 + CD206 + signals, and enhanced tumor apoptosis without obvious systemic toxicity. These results support SeASP H as a promising organic Se-enriched polysaccharide for developing immunomodulatory functional food components.