4.3 Article

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

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ELSEVIER
DOI: 10.1016/j.msec.2021.112103

Keywords

Celastrol; Magnetic Fe3O4/alpha-Fe2O3 heterogeneous nanorods; Liver cancer; Apoptosis; Reactive oxygen species; HIF-1 alpha

Funding

  1. Jiangsu Provincial Postgraduate Scientific Practice and Innovation Project [SJCX20_1432]
  2. Science and Technology Innovation Project of CHN Energy [GJNY-20-109]

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Heterogeneous Fe3O4/alpha-Fe2O3 nanorods were prepared with specific magnetic properties and dimensions, and the surface modification with citric acid and PEG was applied to improve their dispersion in aqueous solution.
Fe3O4/alpha-Fe2O3 heterogeneous nanorods were prepared by a rapid combustion method with alpha-FeOOH nanorods as precursors. Fe3O4/alpha-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 degrees C. Their average length was around 140 nm, and average diameter was about 20 nm. To improve the dispersion characteristics of the Fe3O4/alpha-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/alpha-Fe2O3/CAPEG-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/alpha-Fe2O3/CA-PEG was larger than the non-PEG modified version. Fe3O4/alpha-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/alpha-Fe2O3/CA-PEG-celastrol. Celastrol and Fe3O4/alpha-Fe2O3/CA-PEGcelastrol 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 1 alpha (HIF-1 alpha) was enhanced. We may conclude that celastrol-loaded magnetic Fe3O4/alpha-Fe2O3 heterogeneous nanorods may be applied in the chemotherapy of human cancer with good biocompatibility and delivery.

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