Programmable Atom-Like Nanoparticle Reporters for High-Precision Urinalysis of In Situ Membrane Proteins

Fei Ding, Shuangye Zhang, Qian Chen, Xiaodong Xie, Zhifeng Xi, Zhilei Ge, Xiaolei Zuo, Xiurong Yang, Itamar Willner, Chunhai Fan, Qian Li*, Qiang Xia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The expression of disease-specific membrane proteins (MPs) is a crucial indicator for evaluating the onset and progression of diseases. Urinalysis of in situ MPs has the potential for point-of-care disease diagnostics, yet remains challenging due to the lack of molecular reporter to transform the expression information of in situ MPs into the measurable urine composition. Herein, a series of tetrahedral DNA frameworks (TDFs) are employed as the cores of programmable atom-like nanoparticles (PANs) to direct the self-assembly of PAN reporters with defined ligand valence and spatial distribution. With the rational spatial organization of ligands, the interaction between PAN reporters and MPs exhibits superior stability on cell-membrane interface under renal tubule-mimic fluid microenvironment, thus enabling high-fidelity conversion of MPs expression level into binding events and reverse assessment of in situ MP levels via measurement of the renal clearance efficiency of PAN reporters. Such PAN reporter-mediated signal transformation mechanism empowers urinalysis of the onset of acute kidney injury at least 6 h earlier than the existing methods with an area under the curve of 100%. This strategy has the potential for urinalysis of a variety of in situ membrane proteins.

Original languageEnglish
Article number2310199
JournalAdvanced Materials
Volume36
Issue number11
DOIs
StatePublished - 14 Mar 2024

Bibliographical note

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • DNA framework
  • membrane protein
  • molecular imaging
  • programmable atom-like nanoparticle
  • urinalysis

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