Universal Artificial Urinary Biomarker Probe Enabled by an Aptamer-DNAzyme-Nanozyme Construct.

Area of Science:

• Biomarker Discovery and Diagnostics
• Nanotechnology in Medicine
• Molecular Diagnostics

Background:

• Artificial urinary biomarker probes (AUBPs) are emerging diagnostic tools but are limited to biomarkers with catalytic or high reactivity.
• Early diagnosis of Alzheimer's disease (AD) is crucial and often relies on detecting biomarkers like amyloid-beta oligomers (AβO).

Purpose of the Study:

• To present a general modular design for AUBPs applicable to a wider range of biomarkers.
• To develop and demonstrate an AUBP for sensitive and specific detection of circulating AβO for early AD diagnosis.

Main Methods:

• Designed a modular AUBP integrating aptamer for target recognition, DNAzyme for signal transduction, and nanozyme for signal amplification.
• Developed a proof-of-concept AUBP responsive to amyloid-beta oligomers (AβO).
• Utilized colorimetric urinalysis after nanoprobe injection for detecting circulating AβO levels.

Main Results:

• The developed AUBP specifically and sensitively detected circulating AβO.
• Successfully distinguished AD mice from healthy controls with a low detection limit of approximately 2.8 pg/mL.
• Achieved approximately 67-fold higher sensitivity compared to conventional enzyme-linked immunosorbent assay (ELISA).

Conclusions:

• The novel modular AUBP design expands the applicability of urinary biomarker detection.
• This AUBP approach enables highly sensitive and early diagnosis of Alzheimer's disease through urine analysis.
• The cascaded signal amplification, renal filtration enrichment, and nanozyme catalysis contribute to the enhanced sensitivity.