Catalytically Selective Chemotherapy from Tumor‐Metabolic Generated Lactic Acid

Lactic acid (LA) is a powerful molecule as the metabolic driver in tumor microenvironments (TMEs). Inspired by its high intratumoral level (5–20 µmol g−1), a novel treatment paradigm via the cascade release of H2O2 and ·OH from the LA generated by tumor metabolism is developed for catalytic and pH‐dependent selective tumor chemotherapy. By utilizing the acidity and overexpression of LA within the TME, the constructed lactate oxidase (LOD)‐immobilized Ce‐benzenetricarboxylic acid (Ce‐BTC) metal organic framework enables the intratumoral generation of ·OH via a cascade reaction: 1) the in situ catalytic release of H2O2 from LA by LOD, and 2) the catalytic production of ·OH from H2O2 by Ce‐BTC with peroxidase‐like activity. Highly toxic ·OH effectively induces tumor apoptosis/death. A new strategy for selective tumor chemotherapy is provided herein. Catalytical chemotherapy has recently been recognized as a promising treatment for tumor therapy. Using overexpressed tumor‐metabolic lactic acid as a substrate, the lactate‐oxidase‐immobilized Ce‐benzenetricarboxylic acid metal organic framework triggers the catalytic cascade release of H2O2 and ·OH from lactic acid and enables catalytically and pH‐dependent selective tumor chemotherapy.