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.

Multivalent DNA Flowers for High-Performance Isolation, Detection, and Release of Tumor-Derived Extracellular Vesicles

“…Although various methods have been proposed for isolation and detection of EVs, few have managed to release and recover them, − which is essential for the follow-up biological studies of EVs. Therefore, we subsequently attempted to disintegrate Apt-DFs and release EpCAM + EVs through DNase I.…”

Advanced Nanoencapsulation-Enabled Ultrasensitive Analysis: Unraveling Tumor Extracellular Vesicle Subpopulations for Differential Diagnosis of Hepatocellular Carcinoma via DNA Cascade Reactions

“…Third, traditional enzyme-linked immunosorbent assays (ELISA) not only lack adequate sensitivity but also are susceptible to free target proteins. Additionally, the developed biosensing platforms, such as thermophoresis, − droplet digital PCR, and surface-enhanced Raman scattering (SERS), − often overlook the high heterogeneity of tEVs or the interference of normal cell-derived EVs, thereby compromising the sensitivity and accuracy of tumor diagnosis, especially in differentiating between benign and malignant focal lesions.…”