Small · 2019 · 88 citations · 25 references
MedicineCancer BiologyOncologyChemotherapyMetabolismTumor MicroenvironmentCancer MetabolismMetabolic ReprogrammingMetabolic Reprogramming In CancerTumor Microenvironment ModulationAcidic Tumor MicroenvironmentCatalytic EfficiencyLactic Acid MetabolismMetal-organic Framework CatalystsTumor Acidity ModulationTumor Cell MetabolismTumor Metabolism
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 H 2 O 2 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 H 2 O 2 from LA by LOD, and 2) the catalytic production of ·OH from H 2 O 2 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.
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