Biomimetic self-assembled microspheres based on selenized Angelica-Astragalus compound polysaccharides and platelet membranes for targeted therapy of acute liver injury.

Liver injury remains a major clinical challenge due to the limited bioavailability and potential immunogenicity of conventional therapeutics. Microspheres derived from traditional Chinese medicine (TCM) polysaccharides have attracted increasing attention owing to their biocompatibility and immunoregulatory activities. However, most conventional delivery systems rely primarily on passive accumulation within inflammatory microenvironments, lacking effective injury-targeting capabilities. In this study, we constructed a biomimetic self-assembled microsphere system (Se-AAP/CG/Pm) using selenized Angelica-Astragalus compound polysaccharides (Se-AAP) and cationic gelatin (CG), followed by functionalization with a platelet membrane (Pm) coating via electrostatic adsorption. The resulting microspheres exhibited a nearly spherical morphology, a uniform particle size of 1.5-2 μm, good dispersion stability, and excellent blood compatibility (hemolysis rate < 5%).In vitroevaluation using the MTT assay demonstrated that Se-AAP/CG/Pm microspheres significantly enhanced the metabolic activity of AML-12 hepatocytes and LX-2 hepatic stellate cells while maintaining good cytocompatibility. In a CCl4-induced acute liver injury mouse model, Se-AAP/CG/Pm microspheres markedly reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated hepatocellular necrosis and inflammatory infiltration, and exhibited favorablein vivosafety and hepatoprotective effects. This biomimetic system integrates the bioactivity of selenized TCM polysaccharides with the injury-targeting affinity of platelet membranes, providing a stable and reproducible strategy for platelet membrane-mediated intervention in acute liver injury.