A multifunctional nanocatalytic system based on Chemodynamic-Starvation therapies with enhanced efficacy of cancer treatment

A multi-functional nanocatalytic system based on combined therapies has attracted considerable research attention in recent years due to its potential in the treatment of cancer. Herein, ZnO2@Au@ZIF-67 nanoparticles (NPs) based on hydroxyl radical (•OH) mediated chemodynamic therapy (CDT) and glucose-exhausting starvation therapy (ST) were constructed. Specifically, in the acidic tumor microenvironment (TME), the pH responsive decomposition of the shell ZIF-67 triggered the release of the Fenton-like catalyst Co2+, after which the exposed zinc peroxide (ZnO2) reacted with H2O (H+) to generate O2 and hydrogen peroxide (H2O2). The generated O2 could alleviate hypoxia in the TEM and interact with ultra-small Au NPs originally coated on ZnO2 to catalyze intracellular glucose and to produce another source of H2O2. While the glucose consumption caused the starvation of tumor cells, the generated H2O2 from dual sources reacted with the catalyst Co2+ to generate highly toxic •OH for CDT. Systematic in vitro and in vivo experiments were carried out to evaluate this nanocatalytic system, and the results showed an enhanced efficacy of this cancer therapy.