Catalytically Selective Chemotherapy from Tumor-Metabolic Generated Lactic Acid

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Lactic acid (LA) is a key metabolic driver in tumor microenvironments (TMEs).
• High intratumoral LA levels present therapeutic opportunities.
• Targeting TME acidity and metabolic byproducts is crucial for selective cancer treatment.

Purpose of the Study:

• To develop a novel catalytic and pH-dependent chemotherapy strategy.
• To utilize tumor-generated lactic acid for generating reactive oxygen species (ROS).
• To achieve selective tumor cell apoptosis via ROS-induced damage.

Main Methods:

• Construction of a lactate oxidase (LOD)-immobilized Ce-benzenetricarboxylic acid (Ce-BTC) metal-organic framework.
• Enabling a cascade reaction for ROS generation from intratumoral LA.
• Utilizing the peroxidase-like activity of Ce-BTC for hydroxyl radical (·OH) production.

Main Results:

• The Ce-BTC MOF effectively catalyzed the conversion of LA to hydrogen peroxide (H2O2) and subsequently to highly toxic hydroxyl radicals (·OH).
• The system demonstrated pH-dependent and selective ROS generation within the TME.
• The generated ·OH induced significant tumor apoptosis and cell death.

Conclusions:

• A novel cascade reaction strategy for selective tumor chemotherapy was successfully developed.
• The LOD-Ce-BTC MOF system leverages TME-specific conditions (LA and acidity) for targeted cancer treatment.
• This approach offers a promising new avenue for ROS-based cancer therapy.