Dual-Functional Nanoconfined Metal-Organic Frameworks with Aggregation-Induced Electrochemiluminescence Coupled with DNAzyme Motor for Ultrasensitive miRNA-21 Biosensing.

Abstract

Simultaneously overcoming aggregation-induced quenching and sluggish interfacial kinetics remains a pivotal challenge in electrochemiluminescence. Herein, we have successfully synthesized dual-functional nanoconfined metal-organic frameworks encapsulating Pt-A-COOH complexes (Pt@UiO-67 MOFs) as electrochemiluminescence emitters and co-reaction accelerators by a ligand-similarity-driven doping strategy. The dual-functional Pt@UiO-67 MOFs unlocked aggregation-induced electrochemiluminescence and expedited interfacial reaction kinetics by spatial nanoconfinement, the electrochemiluminescence efficiency of which was ca. 5.4-fold higher than that of the Pt-A-COOH as co-reactant to catalyze the decomposition of S2O8 2-. Density functional theory calculations and electrochemical electron paramagnetic resonance measurements indicated that the nanoconfinement structure reduced the activation energy barrier for the reduction of S2O8 2-, thereby optimizing the kinetics of SO4 •- (0.92 eV) and OH• (0.63 eV) radical generation. Based on the Pt@UiO-67 MOFs and DNAzyme motor, the ultrasensitive biosensor has been successfully constructed and had wide linear range (from ∼10 aM to ∼10 nM) and an ultralow detection limit of ∼4.1 aM. In the preliminary proof-of-concept evaluation using acute kidney injury clinical samples, the assay results had excellent concordance with those of quantitative reverse transcription polymerase chain reaction. This work provides a paradigm integrating supramolecular engineering with DNA nanotechnology, which paves the way for sensitive biodetection and preliminary clinical screening.