Zhihang Ren, Chen Peng, Liu Y, Bingyu Lin, Yunqi Man, Yifu Tan, Liu Z, Qi‐Wen Chen
Nanozymes have attracted considerable attention as chemodynamic therapy (CDT) agents for tumor therapy because of their high catalytic activity. However, their incapable tumor tropism and uncontrollable metabolism interference hinder their further application. Here, a biohybrid system that integrates electroactive bacteria and Fe 2 O 3 nanozyme precursors is introduced to address these challenges. Leveraging the bioactivity of electroactive bacteria, the biohybrids exhibit long-term tumor retention, also in situ catabolize tumor lactate to reduce Fe 2 O 3 into Fe 3 O 4, which mimics peroxidase ability to catalyze the intratumoral H 2 O 2 into cytotoxic hydroxyl radicals and kill tumor cells. The exhaustion of tumor lactate also alleviates tumor cell resistance to oxidative stress by downregulating the oxidative stress-resistant nuclear factor erythroid 2-related factor 2, further amplifying CDT. This study connects the natural bioactivity of living bacteria and the biomimetic catalytic activity of artificial nanozymes to in situ execute CDT and prevent metabolism interference to normal tissues, proposing an innovative strategy for tumor therapy.