Dual endogenous stimulus-responsive Fe3O4@enzymes@ZIF-8 nanocomposites promote enzymatic circulation chemotherapy

Abstract

An APTES-functionalized magnetic core–immobilized enzyme drives the formation of an acid-sensitive ZIF-8 shell via biomineralization growth, which offers a spontaneous dual–endogenous stimulus-responsive modal enzyme catalytic-chemotherapy for HeLa tumor cells. Herein, the ZIF-8 shell plays a dual role in the combination therapy, i.e., protecting activities of embedded enzymes and loading therapeutic agents into the framework. In order to enhance the efficiency of enzyme therapy, a biocascade reaction in confined space via two types of embedded enzymes under endogenous glucose stimuli was performed, which promotes continuous consumption of endogenous glucose, leading to starvation of tumor cells. Simultaneously, the inherent acidic tumor microenvironment and gluconic acid produced from endogenous glucose oxidation can gradually dissociate the ZIF-8 shell with the aid of pH-stimulus-responsive mode to enhance endo-lysosomal escape for releasing therapeutic agents to effectively induce apoptosis of tumor cells. The recovery of the magnetic core can regenerate multifunctional nanoplatforms for achieving circulation therapy of tumor cells.