Self-Localized Plasmonic Nanocavity Strategy for the Glycosylation Detection of Glioblastoma Extracellular Vesicles

The protein glycosylation of extracellular vesicles (EVs) is involved in cellular recognition and emerges as a promising biomarker for cancer diagnosis. However, the lack of efficient labeling and high-resolution detection strategies limits their clinical application. Herein, we developed a self-localized plasmonic nanocavity strategy to analyze the glycosylation characteristics of glioblastoma EVs. First, an engineered phospholipid bilayer structure with a Au nanoring array was designed to capture EVs and induce membrane fusion. Relying on the multifunctional proximity labeling process, a peroxidase-induced proximity labeling was designed to label sialic acid on programmed cell death ligand 1 (PD-L1) of EVs. Based on the identification and labeling process of EVs, the plasmonic nanocavity was self-localized with Au nanocubes and achieved the spontaneous location of MoSe2 QDs. The uniformly enhanced electromagnetic field in the nanocavity resulted in the polarized luminescence signal of MoSe2 QDs for improving the detection sensitivity and resolution. This system demonstrated the precise distinction and sensitive quantification of EV glycosylation in cerebrospinal fluid to distinguish glioblastoma. This research provided a novel strategy for the glycosylation detection of EVs and promoted the clinical application of EVs in glioblastoma diagnosis.