CHA-driven SERS-nanoenzyme sensor for ultra-sensitive diagnosis of gastric precancerous lesions

Early identification and timely intervention of precancerous lesions of gastric cancer are the core strategies to block their malignant transformation into gastric cancer (GC). This study developed a dual functional sensor that combined surface-enhanced Raman scattering (SERS) activity and nanoenzyme catalytic properties. The sensor was driven by catalytic hairpin self-assembly (CHA) technology triggered by the target microRNA-21 (miR-21), promoting the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) and signal amplification of TMB oxidation (ox-TMB). This work used Au-platinum nanoparticles (Au-Pt NPs) as nanozyme probes and silica-encapsulated ferrite (Fe₃O₄@SiO₂) as capture probes. In the presence of target miR-21, CHA technology induced Au-Pt NPs to assemble on the Fe₃O₄@SiO₂ surface, endowing the sensor with SERS enhancement capability and peroxidase-like (POD-like) simulated catalytic performance. This catalyzed the conversion of TMB and hydrogen peroxide (H₂O₂) into the oxidized product ox-TMB with characteristic absorption. CHA technology, acting as an intrinsic driving force for sensor assembly, further facilitated exponential amplification of the ox-TMB detection signal. This SERS sensor demonstrated outstanding detection performance, achieving a detection limit as low as 20.24 aM for miR-21. It also exhibited excellent clinical applicability and accuracy in clinical sample testing. Therefore, the proposed SERS sensor holds significant clinical potential for diagnosing gastric precancerous lesions.