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

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.

Construction of targeted delivery system for curcumin loaded on magnetic α-Fe2O3/Fe3O4 heterogeneous nanotubes and its apoptosis mechanism on MCF-7 cell.

In this work, the magnetic α-Fe2O3/Fe3O4 heterogeneous nanotubes were successfully prepared by solvent hydrothermal-controlled calcination method. The effects of additive concentration, hydrothermal temperature and time on morphology of products were investigated. The α-Fe2O3/Fe3O4 nanotubes with a saturation magnetization of 50 emu/g were prepared calcinated at 600 °C for 4 h using 0.8 g of glucose. Their average length, the outer and inner diameters were around 240 nm, 178 nm and 145 nm, respectively. The α-Fe2O3/Fe3O4 heterogeneous nanotubes coated with water-soluble liposome were applied for targeted delivery of curcumin. The release of curcumin inside the hollow structure of the nanocomposites could be triggered and effectively sustained represented a process of slow release. The encapsulation efficiency of curcumin in the α-Fe2O3/Fe3O4-CUR@LIP nanocomposites reached 82.1 ± 0.9%. MTT assays demonstrated that blank carriers had excellent biocompatibility and application of magnetic field significantly elevated the cytotoxicity of α-Fe2O3/Fe3O4-CUR@LIP nanocomposites on MCF-7 cell. Electrochemical experiment and Prussian blue staining indicated that the α-Fe2O3/Fe3O4@LIP nanocomposites could aggregate in cells to promote the internalization of curcumin. Magnetic α-Fe2O3/Fe3O4-CUR@LIP nanocomposites and curcumin enhanced the expression of reactive oxygen species in MCF-7 cells and induced apoptosis by fluorescence detection. Flow cytometry and western blot verified that the α-Fe2O3/Fe3O4@LIP nanocomposites under magnetic field enhanced cells late-apoptosis by adjusting the expression of apoptosis-related proteins.

Magnetic α-Fe2O3/Fe3O4 Heterostructure Nanorods: Fabrication and Cytotoxicity to A549 Cells.

The magnetic α-Fe2O3/Fe3O4 heterostructure nanorods were fabricated by an alcohol-solution direct combustion method. The influence of the calcination temperature on the composition and properties of the nanorods was investigated. When the calcination temperature was not greater than 400 °C, the magnetic α-Fe2O3/Fe3O4 heterostructure nanorods were obtained, and the saturation magnetization (Ms) of the magnetic α-Fe2O3/Fe3O4 heterostructure nanorods decreased with the calcination temperature increasing from 250 °C to 400 °C; when the calcination temperature was equal or greater than 450 °C, α-Fe2O3 nanorods were obtained. In addition, the effects of nanorods' concentration, nanorods' constituent, incubation time and magnetic field on A549 cytotoxicity were investigated. The cytotoxicity of the heterostructure nanorods appeared time-dependent and concentration-dependent, and the magnetic field could enhance the cytotoxicity of nanorods to A549.

Improved delivery system for celastrol-loaded magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods: HIF-1α-related apoptotic effects on SMMC-7721 cell.

Fe3O4/α-Fe2O3 heterogeneous nanorods were prepared by a rapid combustion method with α-FeOOH nanorods as precursors. Fe3O4/α-Fe2O3 heterogeneous nanorods with a saturation magnetization of 33.2 emu·g-1 were obtained using 30 mL of absolute ethanol at a calcination temperature of 300 °C. Their average length was around 140 nm, and average diameter was about 20 nm. To improve the dispersion characteristics of the Fe3O4/α-Fe2O3 heterogeneous nanorods in aqueous solution, citric acid and PEG were applied to modify the nanorod surface via the Mitsunobu reaction. The results showed that the hydrodynamic size range of Fe3O4/α-Fe2O3/CA-PEG-celastrol was 250-500 nm, the surface potential was -15 mV, and the saturation magnetization was approximately 23 emu·g-1. The drug loading capacity of Fe3O4/α-Fe2O3/CA-PEG was larger than the non-PEG modified version. Fe3O4/α-Fe2O3/CA-PEG-celastrol had slow-release characteristics and was sensitive to changes in pH. Application of a magnetic field significantly promoted the inhibition of SMMC-7721 human liver cancer cell growth after treatment with Fe3O4/α-Fe2O3/CA-PEG-celastrol. Celastrol and Fe3O4/α-Fe2O3/CA-PEG-celastrol increased the production of reactive oxygen species in SMMC-7721 cells and promoted apoptosis and apoptosis-related proteins (p53, Bax, Bcl-2) were also changed. In addition, the expression of hypoxia-inducible factor 1α (HIF-1α) was enhanced. We may conclude that celastrol-loaded magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods may be applied in the chemotherapy of human cancer with good biocompatibility and delivery.