Biomimetic Nanoplatform Based on Macrophage Membrane-Coated Fe3O4 Nanoparticles for Synergistic Ferroptosis and Sonodynamic Therapy of Lung Cancer.

[INTRODUCTION] Triiron tetraoxide nanoparticles (Fe3O4 NPs) effectively induce ferroptosis. However, they are readily identified as foreign by the immune system and undergo rapid clearance from the body via the reticuloendothelial system. Macrophages are a type of phagocytic immune cell. They identify and engulf cancer cells and any foreign entities that lack the specific surface biomarkers of healthy somatic cells. Studies have proposed that camouflaging NPs with macrophage membranes enables effective cancer targeting via cell-cell adhesion mechanisms.

[METHODS] Therefore, we harvested vesicles derived from macrophage membranes and coated them onto the surface of Fe3O4 nanoparticles. This formed a core-shell, biomimetic nanodrug delivery system: Fe3O4@MPs. Subsequently, we loaded hematoporphyrin monomethyl ether (HMME) onto this platform (Fe3O4-HMME@MPs). The nanoparticles were comprehensively characterized. Their in vitro performance, including cellular uptake, reactive oxygen species generation, ferrous ions (Fe) release, and cytotoxicity, was evaluated using A549 lung cancer cells. For in vivo studies, a subcutaneous xenograft model was established in nude mice using A549 cells. The tumor-targeting ability was assessed via fluorescence imaging, and the therapeutic efficacy was systematically evaluated by monitoring tumor volume/weight, histopathological analysis, and immunohistochemical staining (Perls-DAB, TUNEL, Ki67, GPX4).

[RESULTS] Characterization of the NPs, along with in vivo and in vitro experiments, confirmed that Fe3O4-HMME@MPs possess excellent biocompatibility, immune evasion capabilities, and effective targeting of lung tumors. Fe3O4-HMME@MPs treat solid lung tumors through a synergistic of ferroptosis and Sonodynamic therapy.

[CONCLUSION] Our platform provides us with a novel biomimetic strategy, offering a promising approach for clinical translation in lung cancer therapy.