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

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.