Ascorbic Acid-Loaded Nanozymes Enable Self-Supplying H ₂ O ₂ Catalysis and Dual Metal Ion Cycling for Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT) is a tumor treatment that converts endogenous H 2 O 2 into toxic reactive oxygen species (ROS) via Fenton or Fenton-like reactants. It has received much attention because it does not require external energy and has few side effects. However, the therapeutic efficiency of CDT is inhibited by the insufficient supply of H 2 O 2 inside the tumor, thus making it difficult to achieve a satisfactory therapeutic effect. Herein, we designed and synthesized an ascorbic acid (AA)-loaded polyoxometalate-based metal–organic framework nanocomposite (NENU-5) with Mo and Cu ions for Fenton-like reaction centers. On the one hand, AA converts O 2 to H 2 O 2 in vivo to facilitate enhanced ROS production and accelerates the reaction rate of reducing Mo 6+ and Cu 2+ in cells; on the other hand, the reduced Mo 5+ and Cu + in NENU-5 activate Fenton-like reactions. Therefore, NENU-5@AA nanocomposites exhibit a significant inhibitory effect on the tumor cells. Hence, this work effectively addresses the challenges of insufficient H 2 O 2 supply and poor Fenton-like agent regeneration in the tumor microenvironment, thus providing a promising strategy for self-enhanced CDT with potential for clinical applications.