Background and Objectives: Cardiovascular diseases (CVDs) remain a leading cause of mortalityworldwide, with elevated serum cholesterol levels recognized as a primary risk factor. Conventional cholesterol monitoring methods are invasive and intermittent, highlighting the urgent need for noninvasive, real-time monitoring solutions. This study aimed to develop a nanoengineered wearable biosensor platform for accurate, continuous cholesterol monitoring, leveraging the catalytic properties of cerium oxide nanoparticles (CeO2 NPs) integrated into platinum (Pt) electrodes. Cerium oxide nanoparticles were synthesized and stabilized using polyvinylpyrrolidone (PVP) and then immobilized onto Pt electrodes to fabricate a Pt/CeO2 sensing platform. The catalytic oxidation of cholesterol was mediated via the peroxidase-mimetic activity of CeO2 NPs, enabling the detection of hydrogen peroxide through the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). Calibration curves were established across a cholesterol concentration range of 15–100 μM. Validation was performed using human sweat samples from 50 participants, comparing sensor outputs with standard enzymatic colorimetric assays. The biosensor demonstrated high analytical performance, with a limit of quantification (LOQ) of 5.7 μM and a detection sensitivity spanning 15–100 μM. Clinical validation revealed a correlation coefficient (R²) of 0.96 with standard assays, sensitivity of 94.2%, and specificity of 92.8%. The biosensor maintained operational stability under physiological variations, such as pH fluctuations and biofouling, due to engineered antifouling coatings and pH-compensated dual-electrode systems. The developed Pt/CeO2-based wearable biosensor enables noninvasive, accurate cholesterol monitoring in human sweat, offering a promising tool for personalized cardiovascular risk management. Future large-scale validation studies, including expanded demographic diversity and longitudinal assessment, are planned to further establish clinical applicability.
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