Engineering biomimetic ATP-responsive Se-containing core-shell cascade nanozyme for efficient tumor combination therapy

Abstract

The ineffectiveness of cancer chemodynamic treatment (CDT) is intimately connected to intracellular antioxidant defense mechanisms. While great efforts have been made to interfere with the oxidative protection mechanisms within tumor cells, this remains a difficult challenge. Herein, inspired by the glutathione peroxidase (GPx) function for consuming GSH, an artificial selenase was designed to combine with the Fenton reaction to prepare a metal complex nanocarrier (IM-Se-Ph@TA-Fe NPs), in which glucose oxidase (GOx) is loaded to obtain the multienzyme synergic nanozyme GOx@IM-Se-Ph@TA-Fe NPs. In response to the high expression of ATP in the tumor, released GOx could specifically reduce the molecular oxygen to H2O2 by consuming intratumoral glucose and cause tumor starvation. Following that, the generated H2O2 supported the intracellular Fenton reaction and consumed intracellular GSH under the catalysis of selenase to enhance multimodal cancer therapy. The strategy of interfering with the intracellular antioxidant system by utilizing artificial selenase and GOx increases the efficacy of chemodynamic therapy and offers new concepts for cancer combination therapy.