Multienzyme‐Mimic Ultrafine Alloyed Nanoparticles in Metal Organic Frameworks for Enhanced Chemodynamic Therapy

Nanozyme‐based chemodynamic therapy (CDT) has emerged as an effective cancer treatment because of its low side effects and without the requirement of exogenous energy. The therapeutic effect of CDT highlights the pivotal importance of active sites, H2O2 supplement and the glutathione (GSH) depletion of a nanozyme. The construction of a single kind of catalyst with multiple functions for the enhanced CDT is still a big challenge. In this work, seven types of bimetallic nanoparticles are synthesized using a metal–organic framework (MOF) as a stable host instead of a Fenton or Fenton‐like ions supplier. Among them, Cu‐Pd@MIL‐101 with an alloy loading of 9.5 wt% modified by PEG (9.5% CPMP) is found to exhibit the highest peroxidase (POD) like activity combined with a superoxide dismutase (SOD) mimic activity and the function of GSH depletion. The in vivo results suggest that the stable and ultrafine nanoparticles possess favorable CDT effect for tumor and good biosafety as well as biocompatibility. This work has provided a credible strategy to construct nanozymes with an excellent activity and may pave a new way for the design of enhanced tumor CDT treatment. The nanoplatform (named Cu‐Pd@MIL‐101) exhibits an excellent anticancer effect, which is derived from the high activity of peroxidase (POD), superoxide dismutase (SOD), and GSH depletion in an acidic tumor microenvironment (TME). The synergistic effect can produce enough intracellular reactive oxygen species (ROS) to induce tumor cell apoptosis.