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

Abstract 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 Stober 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.