Biological Optical Nanocavity-Coupled Electrochemiluminescence Sensor for the Detection of Extracellular Vesicle Glycosylation in Gastric Cancer Diagnosis

Biological membrane curvature not only signifies morphological characteristics but also participates in various physiological processes. Analyzing the relationship between membrane curvature and biomolecules of extracellular vesicles (EVs) is crucial for understanding their functions. However, it remains challenging to precisely distinguish the characteristics of EVs in specific membrane regions. Herein, we developed a biological optical nanocavity-coupled electrochemiluminescence (ECL) sensor to reveal the correlation between the glycoprotein and membrane curvature of EVs. A curvature-sensitive peptide probe anchored the high curvature membrane of EVs and conducted the proximity ligation with aptamers, enabling the region-specific recognition. By assembling Au NPs onto the membrane surface of EVs, a biological optical nanocavity was constructed, which provided a plasmon coupling effect to enhance the ECL intensity and regulate the polarized emission. The polarized ECL response clearly distinguished both the specific region and molecular distribution of EVs. Our findings indicated that MUC1 with terminal sialylation exhibited preferential distribution in high curvature regions of EV membranes. Furthermore, the detection of EVs in ascites facilitated the diagnosis of peritoneal metastasis in gastric cancer. The proposed ECL sensor achieved sensitive EVs detection with a limit of detection of 3.2 × 10 3 particles mL −1 and the diagnostic accuracy of 95%. Overall, the research provided a sensitive strategy for the analysis of EVs' membrane nano-environment and explored the potential of EVs in assisting clinical diagnosis.