Synergistic cell membrane-coated ECL-DNA biosensor for specificity-enhanced drug lead evaluation.

Cell membrane coating technology has recently emerged as a promising platform for drug activity assessment due to its unique biointerfacing capabilities. Nevertheless, its integration with conventional detection methods such as high performance liquid chromatography (HPLC) and fluorescence probe analysis remains limited by poor specificity and low accuracy, primarily resulting from non-specific adsorption of non-target membrane receptors and interference from background signals. In this study, we presented a collaborative strategy that integrates aptamers with cell membrane coating technology to establish a novel electrochemiluminescence (ECL)-DNA biosensor platform for specifically detecting drug-target receptor interactions. High specificity was achieved through competitive binding between aptamers and drug candidates for membrane receptors, while high accuracy was ensured by employing an ECL detection system incorporating signal cascade amplification and three-dimensional (3D) DNA walkers, enabling reliable performance even with complex biological samples. Using this approach, we demonstrated a linear dynamic range of 1 nmol/L to 2 μmol/L for the detection of desloratadine activity, with a limit of detection (LOD) of 0.16 nmol/L. Furthermore, the platform was successfully applied to evaluate the binding activity of eight drugs to angiotensin-converting enzyme 2 (ACE2), and their pharmacological activities were further characterized. Overall, this aptamer-cell membrane coating synergistic strategy offered excellent specificity and ultra-high sensitivity, making it a valuable tool for elucidating drug-receptor mechanisms of action and providing a robust reference for preclinical drug activity evaluation.