Lewis Acid-Boosted Nanozyme for In Situ Metallization Electrochemical Sensing of Extracellular Vesicles

Extracellular vesicles (EVs) mediate tumor progression by facilitating signal transduction between cancer cells and the microenvironment, positioning them as critical biomarkers for diagnosis. CD20 is a key surface antigen of B cells, and its detection is of great significance for lymphoma detection and therapy monitoring. However, conventional EVs detection methods suffer from high costs, operational complexity, and limited sensitivity. Here, we developed an electrochemical immunosensor utilizing a Lewis acid-boosted nanozyme, Ce/UiO-67, which was synthesized through a one-step hydrothermal method. Ce4+ doping enhances its phosphatase-like activity by mimicking Zn2+–O–Zn2+ active sites, catalyzing the hydrolysis of l-ascorbic acid-2-phosphate (SAP) to ascorbic acid (AA). The resultant AA reduces Ag+ to Ag0 for in situ deposition on the electrode, with the Ag0 oxidation current quantified by differential pulse voltammetry (DPV) for specific CD20 detection on EVs. This sensor achieves a detection range of 5.12 × 102 to 1.6 × 107 particles/μL and a limit of detection (LOD) of 280 particles/μL, offering superior sensitivity and simplicity. Applied to clinical plasma, it distinguishes lymphoma patients from healthy individuals, demonstrating the potential for diagnosis and treatment evaluation.