Non-covalent modification of low-molecular quinones into iron-based nanoreactors enabling self-sustaining Fenton reaction-mediated chemo-dynamic therapy and resisting macrophage uptake

Abstract

Chemo-dynamic therapy of anti-tumor nano-medicine relies on the continuous generation of toxic hydroxyl radical (OH). 2,6-dimethoxy hydroquinone (DMHQ) and 2,6-dimethoxy-ρ-benzoquinone (DMBQ) are potential anti-tumor component in fermented wheat germ. To obtain a self-amplified nanoreactor and cascade cancer therapy, nano Fe3O4 was co-loaded with glucose oxidase and DMHQ + DMBQ. The nanoreactor produced endogenous H2O2 and DMHQ + DMBQ accelerated Fe3+/Fe2+ conversation, thus speeding up the generation of OH. Both in vitro and in vivo antitumor experiments demonstrated enhanced therapeutic efficacy of cancer. Furthermore, an in vitro vein model was used and the results showed that the abundances of stealth-related proteins such as Apolipoprotein B-100 on the surface of the nanoreactors increased in comparison with the nanoreactors without modification of DMHQ and DMBQ, and lower macrophage nonspecific uptake and the expression of inflammatory cytokines of macrophages were found. These findings substantially broaden the biomedical applications of naturally-derived antitumor molecules to nano-catalytic tumor therapy.