Mesoporous silica integrated with Fe3O4 and palmitoyl ascorbate as a new nano-Fenton reactor for amplified tumor oxidation therapy

Abstract

Co-delivery of H₂O₂-generating agent and catalyst via a nano-Fenton reactor to the tumor acidic microenvironment for amplified tumor oxidation therapy has been widely studied. However, high side effects and low efficiency remain the limitations of the design and development of this process. Herein, a new nano-Fenton reactor in which mesoporous silica is integrated with Fe₃O₄ and palmitoyl ascorbate (Fe₃O₄@SiO₂-PA) was designed, with the product exhibiting good dispersion, stability, uniformity and consistent spectral characteristics. The results show that Fe₃O₄@mSiO₂-PA successfully enters cancer cells, significantly inhibits HeLa cells and 3D tumor spheroid growth in vitro via the induction of apoptosis. Meanwhile, Fe₃O₄@mSiO₂-PA administration in vivo markedly suppresses HeLa tumor xenografts growth via the induction of apoptosis, followed by caspase-3 activation and cytochrome C release. Further investigation revealed that Fe₃O₄@mSiO₂-PA causes enhanced production of reactive oxygen species (ROS), which subsequently triggers DNA damage and causes dysfunction of the MAPK and PI3K/AKT pathways. Importantly, Fe₃O₄@mSiO₂-PA shows few side effects and good biocompatibility in vivo. Taken together, these results suggest that Fe₃O₄@mSiO₂-PA inhibits HeLa cell growth in vitro and in vivo by triggering enhanced oxidative damage and regulating multiple signal pathways. Our findings validate the rational design that mesoporous silica integrated with Fe₃O₄ and palmitoyl ascorbate can act as a new nano-Fenton reactor for amplified tumor oxidation therapy.