Biomimetic nanoplatform M-MPDA@CeO2 coated with macrophage membrane in acute lung injury: characterization and function evaluation

Abstract The pathogenesis of acute lung injury (ALI) is characterized by a dysregulated hyperinflammatory cascade initiated by activated pulmonary macrophages. Conventional nanoparticles exhibit limited therapeutic efficacy in ALI due to their insufficient penetration across the pulmonary mucus barrier and inability to inhibit the exacerbated inflammatory cascade within the pathogenic microenvironment. To address these limitations, this study developed a novel macrophage membrane-biomimetic nano-delivery system designed to enhance biocompatibility, achieve targeted delivery to inflammatory sites, and exert synergistic antioxidant effects. The nanocomposite was constructed by loading cerium dioxide (CeO 2 ) nanoparticles onto mesoporous polydopamine (MPDA) and further functionalizing the surface with macrophage membranes through engineering strategies, yielding the M-MPDA@CeO 2 formulation. The physicochemical properties of M-MPDA@CeO 2 was systematically characterized, and its function in reactive oxygen species (ROS) scavenging, antioxidation, macrophage polarization was evaluated in vitro. Using an LPS-induced ALI mouse model, the therapeutic potential of M-MPDA@CeO 2 was assessed in terms of anti-inflammatory and oxidative activities. Results demonstrated that the MPDA@CeO 2 nanocomposite effectively scavenges ROS, alleviates LPS-induced oxidative damage, promotes M2 macrophage polarization, and selectively accumulates at inflammatory sites in ALI. This biomimetic nanoparticle drug delivery system offers a promising strategy for improving ALI treatment, with potential implications for both preclinical research and clinical translation.