Trimetallic CoFeZn nanozymes with enhanced peroxidase-mimetic activity for ultrasensitive electrochemical immunosensing of HE4: Toward ovarian cancer monitoring.

Human epididymis protein 4 (HE4) serves as a crucial biomarker for the early diagnosis and monitoring of ovarian cancer. Herein, a novel trimetallic metal-organic framework (CoFeZn-MOF) was engineered as a peroxidase-mimicking nanozyme, and its application in the development of a sandwich-type electrochemical immunosensor for the highly sensitive detection of HE4 was demonstrated. Compared to single-metal or bimetallic MOFs, CoFeZn-MOF nanozyme exhibited superior peroxidase-like activity, capable of catalyzing the decomposition of hydrogen peroxide while also efficiently oxidizing 3,3',5,5'-tetramethylbenzidine (TMB) to produce the blue oxTMB product. The process of hydrogen peroxide decomposition catalyzed by CoFeZn-MOF involved redox reactions that induced significant electron transfer. Consequently, detectable changes in reduction current occurred within the current-time curve, enabling signal amplification for quantitative analysis of the tumor marker HE4. Under the optimized conditions, the linear detection range of the immunosensor was 0.01-800 ng/mL, with a low detection limit of 4.6 pg/mL. In addition, the biosensor exhibited outstanding stability, reproducibility, and interference resistance. Furthermore, through the analysis of actual samples, the constructed biosensor had great potential in clinical applications, providing a novel high-sensitivity analytical tool for tumor marker detection.