Programmable DNAzyme nanocatalysts for tumor immunometabolic modulation

Area of Science:

• Biotechnology and Nanomedicine
• Catalytic Nucleic Acids
• Immunometabolism

Background:

• Programmable RNA-cleaving DNAzymes (RCDs) are catalytic nucleic acids with enzyme-like activity.
• Traditionally used for gene regulation, DNAzymes are now advanced as biosensing modules.
• Nanotechnology integration enhances DNAzyme functionality for stimuli-responsive applications.

Purpose of the Study:

• To review the mechanistic foundations of DNAzyme catalysis.
• To summarize nanoengineering strategies for programmable sensing and stimuli-responsive DNAzymes.
• To discuss the bridging of biosensing and catalytic immunometabolic functions.

Main Methods:

• Integration of DNAzymes into metal-oxide scaffolds, DNA-framework architectures, and metal-organic frameworks.
• Engineering hybrid platforms to create confined catalytic microenvironments and responsive activation.
• Utilizing DNAzyme nanocatalysts for selective cleavage of metabolic and immune-regulatory transcripts.

Main Results:

• Engineered DNAzyme systems function as nanoscale biosensors responding to biological cues (pH, redox, ions, microRNA).
• DNAzyme nanocatalysts reprogram tumor immunometabolism by altering glycolysis, redox balance, and mitochondrial activity.
• Metabolic reprogramming alleviates immunosuppression and promotes innate and adaptive immune activation.

Conclusions:

• Programmable DNAzyme nanocatalysts offer enhanced analytical performance in biosensing.
• These platforms can reshape tumor immunometabolism, leading to anti-tumor immune responses.
• DNAzyme nanocatalysts represent promising preclinical platforms for biosensing-guided immunometabolic intervention.