Effect and mechanism of paclitaxel loaded on magnetic Fe₃O₄@mSiO₂-NH₂-FA nanocomposites to MCF-7 cells

Abstract

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.

Keywords:

• Antitumor
• targeted nanoformulation
• Fe₃O₄
• paclitaxel
• nanoparticle

Disclosure statement

The authors declare no competing financial interest.

Author contributions

Yun Ni: Conceptualization, Methodology, Writing-Original Draft. Peng Deng: Investigation, Data Curation, Formal analysis. Ruitong Yin: Visualization, Project administration. Ziye Zhu: Validation, Software. Chen Ling: Resources, Visualization. Mingyi Ma: Investigation, Project administration. Jie Wang: Investigation, Resources. Shasha Li: Validation, Writing - Review & Editing. Ruijiang Liu: Conceptualization, Writing - Review & Editing, Supervision, Funding acquisition.

Data availability statement

The data and materials generated and analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Jiangsu Provincial Postgraduate Scientific Practice and Innovation Project (Grant No. SJCX21_1722) and the Science and Technology Innovation Project of CHN Energy (Grant No. GJNY-20-109).