Ascorbic Acid-Loaded Nanozymes Enable Self-Supplying H₂O₂Catalysis and Dual Metal Ion Cycling for Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT) is a tumor treatment that converts endogenous H₂O₂ 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 H₂O₂ 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 O₂ to H₂O₂ in vivo to facilitate enhanced ROS production and accelerates the reaction rate of reducing Mo⁶⁺ and Cu²⁺ in cells; on the other hand, the reduced Mo⁵⁺ 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 H₂O₂ 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.