Synthetic urinary biomarker probes for disease detection and monitoring

Abstract

Owing to their noninvasive nature and convenient accessibility, urine-based detection methods hold great promise for enabling early diagnosis, which is essential for precision clinical intervention and improving therapeutic outcomes. However, conventional urine biomarker analysis faces critical challenges, including low abundance, short half-life, and interference from background signals, which limit sensitivity and reliability. To address these limitations, Synthetic Urinary Biomarker Probes (SUBPs) have emerged to interact with disease biomarkers as an active diagnostic strategy. Through programmable molecular designs, SUBPs amplify weak signals originating from specific biomarkers in vivo and convert them into stable reporter molecules excreted in urine, thereby providing a novel and sensitive platform for noninvasive disease detection. In this Review, we first outline the fundamental concepts of SUBPs and highlight their advantages over traditional endogenous urinary biomarkers. We then systematically discuss their modular design principles, including disease-responsive modules, programmable reporter units, and scaffolds. Finally, we provide a detailed overview of representative applications spanning multiple diseases, followed by a discussion of the opportunities and challenges associated with their clinical translation.