Biocatalytic cascade in tumor microenvironment with a Fe2O3/Au hybrid nanozyme for synergistic treatment of triple negative breast cancer

Designing nanozyme hybrids with cascade catalytic activities and coupling effects has significant promises in tumor therapy through concerted effects. In this work, a goethite-derived porous Fe2O3/Au hybrid nanozyme was fabricated for synergistic treatment of triple negative breast cancer. The as-prepared porous Fe2O3 nanoparticle exhibits excellent peroxidase-like activity compared to goethite particles, which can generate hydroxyl radicals in the tumor microenvironment. Furthermore, the Fe2O3 nanoparticle induces ferroptosis through intracellular lipoperoxide accumulation. After decorating glucose oxidase-mimicking gold nanoparticles, the Fe2O3/Au hybrid nanozyme is able to catalyze glucose into gluconic acid and H2O2. The glucose consumption deprives the energy of the tumor cell, and the generated H2O2 can be converted to hydroxyl radicals through the biocatalytic reaction. Importantly, the coupling of gold nanoparticles enhances the photothermal conversion of the porous Fe2O3 nanoparticle. Thus, the designed Fe2O3/Au hybrid nanozyme can be used for tumor therapy through starvation, cascade catalytic reactions, ferroptosis, and photothermal manners. This work presents a derivative method that transforms minerals into nanozyme and couples nanozymes for synergistic tumor therapy, shedding light on the rational design of nanozyme composites for biomedicine.