Automatic metabolism modulator for glycolytic intervention‐induced cascade cancer therapy

Abstract

Effective intervention in glycolytic metabolism is a promising way to inhibit tumor malignant invasion. However, the inherent hypoxia environment and unitary regulating model subsequently compromise its therapeutic efficacy. Herein, a facile way to design an automatic metabolism modulator (auto‐MMOD) is developed by loading glucose oxidase (GOx) and DNA‐templated silver nanoclusters (DNA‐AgNCs) into a pH‐responsive zeolitic imidazolate frameworks‐8 (ZIF‐8) nanocarrier, which can activate a cascaded metal ion‐killing effect during GOx‐regulated glycolysis metabolism. When the acidic lysosome microenvironment induces ZIF‐8 decomposition, the released GOx can effectively consume glucose and generate H2O2, thus inhibiting Adenosine Triphosphate synthesis and accelerating tumor starvation. Moreover, the released Ag+ in response to H2O2 can disturb bioenergy metabolism to inhibit tumor proliferation, which further enhances the tumor‐killing effect in hypoxic microenvironments. This study achieves effective tumor suppression in vitro and in vivo by integrating ion therapy into glycolysis intervention, which establish a promising strategy for nano‐theranostics.