Magnetic Fe₃O₄ nanoparticles were prepared via a simple hydrothermal method and utilized to load paclitaxel. The average particle size of Fe₃O₄ nanoparticles was found to be 20.2 ± 3.0 nm, and the calculated saturation magnetization reached 129.38 emu/g, verifying superparamagnetism of nanomaterials. The specific surface area and pore volume were 84.756 m²/g and 0.265 cm³/g, respectively. Subsequently, Fe₃O₄@mSiO₂ nanoparticles were successfully fabricated using the Fe₃O₄ nanoparticles as precursors with an average size of 27.81 nm. The relevant saturation magnetization, zeta potential, and specific surface area of Fe₃O₄@mSiO₂-NH₂-FA were respectively 76.3 emu/g, −14.1 mV, and 324.410 m²/g. The pore volume and average adsorption pore size were 0.369 cm³/g and 4.548 nm, respectively. Compared to free paclitaxel, the solubility and stability of nanoparticles loaded with paclitaxel were improved. The drug loading efficiency and drug load of the nanoformulation were 44.26 and 11.38%, respectively. The Fe₃O₄@mSiO₂-NH₂-FA nanocomposites were easy to construct with excellent active targeting performance, pH sensitivity, and sustained-release effect. The nanoformulation also showed good biocompatibility, where the cell viability remained at 73.8% when the concentration reached 1200 μg/mL. The nanoformulation induced cell death through apoptosis, as confirmed by AO/EB staining and flow cytometry. Western blotting results suggested that the nanoformulation could induce iron death by inhibiting Glutathione Peroxidase 4 (GPX4) activity or decreasing Ferritin Heavy Chain 1 (FTH1) expression. Subsequently, the expression of HIF-1α was upregulated owing to the accumulation of reactive oxygen species (ROS), thus affecting the expression of apoptosis-related proteins regulated by p53, inducing cell apoptosis.

A novel type of magnetic α-Fe₂O₃/Fe₃O₄ heterogeneous nanoparticles was prepared via a facile solution combustion process with ferric nitrate and urea as raw materials, and they were characterized by XRD, SEM, TEM, and VSM techniques. The effects of the calcination temperature, the calcination time, the ratio of ferric nitrate and urea, and the heating rate on the relative content of Fe₃O₄ in the heterogeneous nanoparticles were investigated. The toxicity of α-Fe₂O₃/Fe₃O₄ heterogeneous nanoparticles to human hepatocytes L-02, the blood routine, and the histopathological section observation of mice were explored. The results showed that the ratio of ferric nitrate and urea was a key factor to affect the relative content of Fe₃O₄ in the heterogeneous nanoparticles. The calcination temperature and the calcination time had similar influences, and the corresponding calcination temperature and the calcination time were selected according to their own needs. The CCK8 results initially revealed that α-Fe₂O₃/Fe₃O₄ heterogeneous nanoparticles had no effect on cell viability when the concentration of the heterogeneous nanoparticles was less than 100 ng/mL, which suggested their excellent biocompatibility. At the same time, the tail vein administration concentration of 0.9 mg/kg had good biological safety.