Catalytically Selective Chemotherapy from Tumor‐Metabolic Generated Lactic Acid

Abstract

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 H₂ O₂ 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 H₂ O₂ from LA by LOD, and 2) the catalytic production of ·OH from H₂ O₂ 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.