Catalytically Selective Chemotherapy from Tumor-Metabolic Generated Lactic Acid

Small. 2019 Nov;15(46):e1903746. doi: 10.1002/smll.201903746. Epub 2019 Sep 25.

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.

Keywords: catalytic tumor chemotherapy; cerium; lactic acid; reactive oxygen species; tumor microenvironments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Catalysis
  • Cell Death
  • Cerium / chemistry
  • Enzymes, Immobilized / metabolism
  • Hep G2 Cells
  • Humans
  • Lactic Acid / metabolism*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mixed Function Oxygenases / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Tricarboxylic Acids / chemistry

Substances

  • Antineoplastic Agents
  • Enzymes, Immobilized
  • Tricarboxylic Acids
  • Cerium
  • Lactic Acid
  • Mixed Function Oxygenases
  • lactate 2-monooxygenase
  • trimesic acid