Spatially asymmetric cascade nanocatalysts for enhanced chemodynamic therapy

Chemodynamic therapy (CDT) based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy. However, most of the reported cascade catalytic systems are designed based on symmetric- or co-assembly of multiple catalytic active sites, in which their functions are difficult to perform independently and may interfere with each other. Especially in cascade catalytic system that involves fragile natural-enzymes, the strong oxidation of free-radicals toward natural-enzymes should be carefully considered, and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity. Herein, a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT, which is composed by a Fe₃O₄ head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase (mSiO₂-GOx). The mSiO₂-GOx subunit could effectively deplete glucose in tumor cells, and meanwhile produce a considerable amount of H₂O₂ for subsequent Fenton reaction under the catalysis of Fe₃O₄ subunit in the tumor microenvironment. Taking the advantage of the spatial isolation of mSiO₂-GOx and Fe₃O₄ subunits, the catalysis of GOx and free-radicals generation occur at different domains of the asymmetric nanocomposite, minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side. In addition, direct exposure of Fe₃O₄ subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives. So, compared with traditional core@shell structure, the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%, thus realizing improved cancer cell killing and tumor restrain efficiency.