In Situ Electroactive Bacteria-Activated Nanozyme for Amplifying Chemodynamic Therapy of Solid Tumors.

Abstract

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 Fe₂O₃ nanozyme precursors is introduced to address these challenges. Leveraging the bioactivity of electroactive bacteria, the biohybrids exhibit long-term tumor retention, also <i>in situ</i> catabolize tumor lactate to reduce Fe₂O₃ into Fe₃O₄, which mimics peroxidase ability to catalyze the intratumoral H₂O₂ 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 <i>in situ</i> execute CDT and prevent metabolism interference to normal tissues, proposing an innovative strategy for tumor therapy.