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 Fe_(3)O_(4)head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase(mSiO_(2)-GOx).The mSiO_(2)-GOx subunit could effectively deplete glucose in tumor cells,and meanwhile produce a considerable amount of H_(2)O_(2)for subsequent Fenton reaction under the catalysis of Fe_(3)O_(4)subunit in the tumor microenvironment.Taking the advantage of the spatial isolation of mSiO_(2)-GOx and Fe_(3)O_(4)subunits,the catalysis of GOx and freeradicals 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 Fe_(3)O_(4)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.