Tumor‐Microenvironment‐Responsive Cascade Reactions by a Cobalt‐Single‐Atom Nanozyme for Synergistic Nanocatalytic Chemotherapy

Abstract Nanocatalytic therapy, involving the nanozyme‐triggered production of reactive oxygen species (ROS) in the tumor microenvironment (TME), has demonstrated potential in tumor therapy, but nanozymes still face challenges of activity and specificity that compromise the therapeutic efficacy. Herein, we report a strategy based on a single‐atom nanozyme to initiate cascade enzymatic reactions in the TME for tumor‐specific treatment. The cobalt‐single‐atom nanozyme, with Co−N coordination on N‐doped porous carbon (Co‐SAs@NC), displays catalase‐like activity that decomposes cellular endogenous H 2 O 2 to produce O 2 , and subsequent oxidase‐like activity that converts O 2 into cytotoxic superoxide radicals to efficiently kill tumor cells. By incorporation with doxorubicin, the therapy achieves a significantly enhanced antitumor effect in vivo. Our findings show that cascade TME‐specific catalytic therapy combined with chemotherapy is a promising strategy for efficient tumor therapy.