Delivery of apigenin-loaded magnetic Fe₂O₃/Fe₃O₄@mSiO₂ nanocomposites to A549 cells and their antitumor mechanism

This study introduces a mesoporous magnetic nano-system for the delivery of apigenin (API). A targeted therapeutic drug delivery system was prepared based on Fe₂O₃/Fe₃O₄@mSiO₂-HA nanocomposites. Magnetic Fe₂O₃/Fe₃O₄ heterogeneous nanoparticles were first prepared via the rapid-combustion process. The effects of solvent type, solvent volume, calcination temperature, and calcination time on the crystal size and magnetism of the Fe₂O₃/Fe₃O₄ heterogeneous nanoparticles were investigated. The mesoporous silica shell was deposited on the Fe₂O₃/Fe₃O₄ heterogeneous nanoparticles using an improved Stöber method. HA was exploited as the targeting ligand. The specific surface area of the Fe₂O₃/Fe₃O₄@mSiO₂ nanocomposites was 369.6 m²/g, which is 19 times higher than that of the magnetic Fe₂O₃/Fe₃O₄ heterogeneous nanoparticle cores. Drug release properties from the Fe₂O₃/Fe₃O₄@mSiO₂-HA nanocomposites were studied, and the result showed that API-loaded nano-system had sustained release effect. Prussian blue staining and electrochemical performance variation showed that an external magnetic field facilitated cell uptake of Fe₂O₃/Fe₃O₄@mSiO₂-HA nanocomposites. MTT assays showed that the cell inhibition effect of API-Fe₂O₃/Fe₃O₄@mSiO₂-HA was stronger than that of free API at the same drug dose under a magnetic field and Fe₂O₃/Fe₃O₄@mSiO₂-HA nanocomposites showed good biocompatibility. Fluorescence imaging, flow cytometry, western blot, reactive oxygen species (ROS), Superoxide dismutase (SOD) and malondialdehyde (MDA) kits verified that the enhanced therapeutic action was due to the promotion of apoptosis, lipid peroxidation, and ferroptosis. The magnetic nano-system (Fe₂O₃/Fe₃O₄@mSiO₂-HA) showed good magnetic targeting and active hyaluronic acid targeting, and has the potential to provide a targeted delivery platform for many antitumor drugs.