Lactate-Modulating Nanozyme-Mediated Mitochondrial Respiration Block for Tumor Immunosuppression Remodeling

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Abnormal lactate metabolism in tumors promotes immune escape within the tumor microenvironment.
• Conventional lactate-targeted therapies face limitations including short half-life and insufficient lactate consumption.

Purpose of the Study:

• To design a novel nanocatalytic medicine for effective lactate metabolism intervention in tumors.
• To overcome limitations of existing lactate-targeted therapies by blocking downstream pyruvate influx.

Main Methods:

• Engineered carbondoping copper nitride nanozyme (Cu3N-C NE) with enhanced lactate oxidase (LOX) activity.
• Computational analysis of lactate metabolism modulation via hydrogen atom transfer (HAT) mechanism.
• In situ downregulation of tumor lactate levels and blocking of pyruvate mitochondrial respiration.

Main Results:

• Cu3N-C NE demonstrated enhanced LOX activity, facilitating lactate breakdown.
• Carbondoping promoted lactate metabolism by activating specific C-H bonds via HAT.
• The nanomedicine effectively remodeled the immunosuppressive tumor microenvironment by reducing lactate and blocking pyruvate influx.

Conclusions:

• The developed Cu3N-C NE represents a next-generation nanomedicine for lactate modulation in cancer.
• This approach offers a promising strategy to reprogram tumor lactate metabolism and enhance anti-tumor immunity.
• The study provides a proof-of-concept for heteroatom-doping in nanomedicine design with potential industrial applications.