Zinc–Adenine Metal‐Organic Frameworks for Electrochemical Detection of VCAM‐1 ⁺ CD63 ⁺ Endothelial Cell‐derived Extracellular Vesicles

ABSTRACT Early detection of vascular inflammation is critical for preventing cardiovascular diseases (CVDs), yet conventional biomarkers often fail to capture endothelial activation at its onset. Here, we report a dual‐aptamer biosensing platform that integrates CD63 aptamer–functionalized zinc–adenine metal–organic frameworks (CD63@ZnMOFs) for extracellular vesicle (EV) isolation with vascular cell adhesion molecule‐1 (VCAM‐1) aptamer–modified screen‐printed gold electrodes for electrochemical detection of VCAM‐1 + CD63 + EVs. The CD63@ZnMOF particles enable efficient and gentle capture of total EVs under aqueous conditions, concentrating the target biomarker and eliminating serum interference prior to detection. Differential pulse voltammetry and electrochemical impedance spectroscopy clearly demonstrated concentration‐dependent responses across 10 7– 10 9 EVs/mL ( R 2 = 0.99). The assays exhibited excellent specificity, distinguishing VCAM‐1 + CD63 + EVs from negative controls, and effectively discriminated between healthy and spiked serum samples. This hybrid ZnMOF–aptamer design provides a modular, label‐free, and anti‐fouling strategy for sensitive detection of endothelial‐derived EVs, offering a promising platform for early diagnosis and monitoring of CVDs.