Macrophage Membrane-Camouflaged Mesoporous Polydopamine Nanoparticles for Targeted Delivery of Apigenin in Sepsis-Induced Acute Lung Injury

Introduction: Sepsis-induced acute lung injury (ALI) is a critical illness that poses a serious threat to human health, and effective treatments remain lacking. This study aimed to develop a macrophage membrane-biomimetic nano-delivery system loaded with mesoporous polydopamine (MPDA)-encapsulated apigenin (API) and to investigate its therapeutic potential in ALI. Methods: In this study, we developed a macrophage membrane-coated biomimetic nano-delivery system, designated MEM@MPDA/API nanoparticles (NPs). We first systematically characterized the physicochemical properties of MEM@MPDA/API, and then evaluated its cellular uptake, reactive oxygen species (ROS) scavenging capacity, and mitochondrial function restoration through in vitro experiments. In vivo, after constructing an ALI mouse model, we assessed its active targeting to lung tissue, anti-inflammatory efficacy, pulmonary barrier repair capacity, and tissue safety following tail vein administration. Results: In vivo results demonstrated that MEM@MPDA/API NPs effectively scavenged ROS, reduced inflammatory cytokine levels, and restored mitochondrial function. In the ALI mouse model, these NPs efficiently accumulated in the injured lung regions, alleviated pulmonary histopathological damage, and repaired the alveolar epithelial barrier. Integrated single-cell transcriptomics analysis and network pharmacology studies revealed that mitophagy-related pathways were activated during the progression of ALI. Conclusion: This study proposes a promising biomimetic nano-delivery strategy, providing a safe and efficient potential new approach for the application of biomimetic nanomedicine in the treatment of ALI and oxidative stress-related critical diseases.