Controlled Nanozyme-Substrate Accessibility for Ultrasensitive Electrochemical Detection of miRNA

Area of Science:

• Biochemistry
• Nanotechnology
• Molecular Biology

Background:

• MicroRNAs (miRNAs) are crucial disease biomarkers.
• Existing detection methods are complex, enzyme-dependent, and lack sensitivity for small molecules.
• One-step electrochemical methods show limited signal changes due to miRNA size and nanozyme background signals.

Purpose of the Study:

• To develop a highly sensitive and specific one-step electrochemical detection system for miRNAs.
• To overcome the limitations of weak signal changes and high background noise in current miRNA detection methods.
• To introduce a novel strategy based on controlled nanozyme-substrate accessibility.

Main Methods:

• A ferrocene (Fc)/Au/DNA composite was used as a signal-shielding layer.
• This layer controlled the accessibility of H2O2 to the graphene oxide/high-entropy alloys (GO/HEAs) nanozyme.
• Electrochemical detection was employed to measure miRNA binding events.

Main Results:

• The strategy effectively suppressed background signals by controlling·OH generation.
• Signal suppression was markedly enhanced after miRNA binding, improving signal difference.
• The developed sensor achieved a highly sensitive detection limit of 1.67 fM for miR-125b.
• The method demonstrated high sensitivity and specificity for miRNA discrimination.

Conclusions:

• The controlled nanozyme-substrate accessibility strategy offers a new concept for sensitive miRNA detection.
• This approach enhances signal discrimination, overcoming limitations of previous methods.
• The developed biosensor provides a promising tool for early disease diagnosis through miRNA biomarker analysis.