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  • Review Article
  • Published:

Artificial urinary biomarker probes for diagnosis

Abstract

Urinalysis is a widely used medical test for healthcare monitoring and disease diagnosis. However, traditional urinalysis relies on endogenous biomarkers that have limited diagnostic sensitivity and specificity. To address these issues, molecular optical probes have been engineered to interact with disease biomarkers in vivo and produce artificial urinary biomarkers (AUBs). AUBs are then excreted into urine for the remote detection of diseases through urinalysis. In this Review, we first introduce AUB probes and highlight the benefits of AUBs over endogenous urinary biomarkers. We then discuss the design principles of two categories of these probes, namely, intrinsic AUB probes and AUB-secreting nanoprobes, with their corresponding detection modalities in urine test. Finally, we summarize the applications of AUB probes in disease diagnostics and discuss the current challenges and strategies to advance their clinical translation.

Key points

  • Current urinalysis tests using endogenous biomarkers suffer from low biomarker concentration and poor specificity.

  • AUBPs are a new class of molecular imaging probes designed to interact with disease-associated biomarkers, which release AUBs that are remotely and readily detectable in urine.

  • AUBPs consist of intrinsic probes and AUB-secreting nanoprobes tailored to different disease biomarkers, administration routes and in vivo pharmacokinetics.

  • AUBs possess unique optical, mass, biological and catalytic properties, which render AUBs distinguishable from endogenous substances in urine.

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Fig. 1: AUBP-based urinalysis for disease diagnosis.
Fig. 2: Design of AUBPs.
Fig. 3: AUB properties and detection methods for urinalysis.
Fig. 4: AUBP-based diagnosis of organ injury.
Fig. 5: AUBP-based diagnosis of cancer.
Fig. 6: AUBP-based diagnosis of disease-related immunity.

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Acknowledgements

K.P. thanks the Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005) for the NRF Investigatorship Award.

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Xu, C., Pu, K. Artificial urinary biomarker probes for diagnosis. Nat Rev Bioeng (2024). https://doi.org/10.1038/s44222-024-00153-w

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