DNA‐Guided Extracellular‐Vesicle Metallization with High Catalytic Activity for Accurate Diagnosis of Pulmonary Nodules

Abstract Sensitive and specific analysis of extracellular vesicles (EVs) offers a promising minimally invasive way to identify malignant pulmonary nodules from benign lesions. However, accurate analysis of EVs is subject to free target proteins in blood samples, which compromises the clinical diagnosis value of EVs. Here a DNA‐guided extracellular‐vesicle metallization (DEVM) strategy is described for ultrasensitive and specific analysis of EV protein biomarkers and classification of pulmonary nodules. The facile DEVM process mainly includes the incorporation of DNA labeled with cholesterol and thiol groups into EV membranes and subsequent deposition of Au³⁺ and Pt⁴⁺ to allow the DNA‐functionalized EVs to be encapsulated with AuPt nanoshells. It is found that the synthesized AuPt‐metallized EVs possess extrinsic peroxidase‐like activity. Utilizing the feature of the catalytic metal nanoshells just growth on the EV membranes, the DEVM method enables multiparametric recognition of target proteins and EV membranes and can produce an amplified colorimetric signal, avoiding the interference of free proteins. By profiling four surface proteins of EVs from 48 patients with pulmonary nodules, the highest area under the receiver operating characteristic curve (0.9983) is obtained. Therefore, this work provides a feasible EVs analysis tool for accurate pulmonary nodules management.