Allosteric Regulation of Spherical Nucleic Acid for Facile Discrimination of Patients with Different Heart Failure Severity

Heart failure (HF) is a rising global cardiovascular epidemic with poor quality of life and high mortality; therefore, molecular biomarker-based facile diagnosis and risk prediction of HF disease could provide a unique window into predicting adverse clinical outcomes and enabling timely intervention. Rapid and sensitive quantification of HF-related bioindicators in point-of-care (POC) settings could further improve the diagnosis and management of HF. Herein, a robust spherical nucleic acid (SNA) aptasensor is proposed for the accurate detection of N-terminal pro-brain natriuretic peptide (NT-proBNP), a gold-standard biocandidate in HF. In this assay, the aptamer can specifically recognize the NT-proBNP target and expose the presealed symmetric fragments. The unlocked symmetric fragments initiate the self-hybridized SNAs by base-pairing, resulting in the aggregation of SNAs and producing a color change from red to blue for the visual detection of NT-proBNP. By integrating the self-hybridization acceleration assembly, the aggregation of SNAs can be accomplished in approximately 20 min, facilitating the on-site detection of NT-proBNP. Compared to the hospital-adopted fluorescence immunochromatography assay (FICA), our SNA aptasensor revealed better specificity (96.0% vs 76.0%), diagnostic accuracy (90.0% vs 88.0%), and positive predictive value (PPV) (95.4% vs 80.6%). Leveraging the programmable allosteric properties of DNA-based aptamers for signal transduction, risk stratification in patients with HF is well established by our SNA aptasensor with a sufficiently high accuracy (96.0%). We anticipate that this allosteric modulation of the SNA aptasensor has the potential to facilitate sensitive and facile disease diagnosis, therapeutic evaluation, and prognosis.