Ultrasensitive electrochemical detection of neuron-specific enolase based on spiny core-shell Au/Cu_xO@CeO₂ nanocubes

As a specific biomarker, neuron-specific enolase (NSE) is an essential clinical indicator for diagnosing small cell lung cancer. In this paper, a sandwich-type electrochemical immunosensor was designed for the quantitative detection of NSE. AuPt nanoblock spherical nanoarchitectonics (AuPt NSNs), a bimetallic nanoparticle with a rugged morphology, were utilized as the substrate, which could enhance the electronic conduction and increase the immobilization capacity of the primary antibody (Ab₁). Moreover, through a simple hydrothermal method, Au/Cu_xO@CeO₂ was prepared as a spiny core-shell nanocube with cerium dioxide (CeO₂) and gold nanoparticles (Au NPs) loading. The combination of Cu₂O, CuO, and CeO₂ showed favorable catalytic activity toward hydrogen peroxide (H₂O₂). Furthermore, the deposition of Au NPs on the spiny surface structure enhanced the specific surface area and biocompatibility, thereby rendering it more effective for loading the second antibody (Ab₂). As the label material, the Au/Cu_xO@CeO₂ achieved signal amplification and sensitive detection with the immunosensor. Under optimal conditions, the designed immunosensor possessed a broad linear range of 50 fg mL^-1 to 100 ng mL^-1 and a limit of detection of 31.3 fg mL^-1, along with satisfactory performance in sensitivity, selectivity, and stability.