Ultrasensitive Electrochemiluminescence Aptasensor With DNA Nanotetrahedron Amplification for Multilevel Detection of cTnI From Cells to Patients

ABSTRACT Accurate detection of myocardial injury (MI) biomarkers for assessing anticancer drug‐induced cardiotoxicity has long been constrained by insufficient capture efficiency and limited assay sensitivity. To address this challenge, we developed an electrochemiluminescence (ECL) aptasensor for the detection of cardiac troponin I (cTnI) based on a two‐step sequential assembly strategy. DNA nanotetrahedron (NTH)‐ assembled aptamers were immobilized onto magnetic beads to form multivalent capture probes for efficient target enrichment via magnetic separation. Meanwhile, a synergistic signal probe was constructed by functionalizing terbium‐based metal–organic frameworks (Tb‐MOF) loaded with cadmium sulfide quantum dots (CdS QDs) with single‐stranded aptamers. Specific recognition of cTnI forms a sandwich‐like complex, generating a robust ECL signal for quantitative readout. A systematic comparison between one‐step and two‐step incubation formats revealed that the latter offers a wider linear range and a lower detection limit (0.04 pg mL −1 ), owing to its cleaner binding environment and reduced steric interference. Importantly, the platform was successfully applied to quantify target cTnI at cellular, animal, and clinical sample levels, demonstrating the capability for multilevel detection of drug‐induced MI. These findings establish a reliable tool for evaluating drug‐induced MI with high sensitivity and translational versatility, advancing precision medicine in cancer therapy.