Highly dispersed nano-enzyme triggered intracellular catalytic reaction toward cancer specific therapy

Currently, reactive oxygen species (ROS)-induced apoptosis systems have drawn increasing attention in cancer therapy, owing to their specific tumor inhibition ability and great biocompatibility. Herein, we developed a highly dispersed nano-enzyme based on the assembly of natural glucose oxidase (GOD) onto CoFe-layered double hydroxides (CoFe-LDHs) monolayer nanosheets. By virtue of the high dispersion of Fe³⁺ within the host layer, the CoFe-LDHs nanosheets exhibit a collaborative enhanced Fenton catalytic activity with a rate constant of 3.26 × 10^-4 s^-1, which is 1-3 orders of magnitude higher than other iron-containing Fenton reaction agents. Subsequently, with a massive H₂O₂ triggered by GOD, GOD/CoFe-LDHs nanohybrid converts a cascade of glucose into hydroxyl radicals under tumor acid conditions, which is validated by a high maximum velocity (V_max = 2.23 × 10^-6 M) and low Michaelis-Menten constant (K_M = 5.40 mM). Through the intracellular catalytic Fenton reaction within the tumor environment, both in vitro and in vivo results demonstrate the excellent antitumor effect of GOD/CoFe-LDHs. Therefore, a self-supplied, ultra-efficient and sequential catalytic tumor-specific therapy has been achieved based on GOD/CoFe-LDHs nano-enzyme, which holds great promise in clinical cancer therapy with minimum side effects.