Effect and mechanism of paclitaxel loaded on magnetic Fe <sub>3</sub> O <sub>4</sub> @mSiO <sub>2</sub> -NH <sub>2</sub> -FA nanocomposites to MCF-7 cells
Yun Ni, Peng Deng, Ruitong Yin, Ziye Zhu, Chen Ling, Mingyi Ma, Jie Wang, Shasha Li, Ruijiang Liu
Abstract
-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.