Small extracellular vesicles (sEVs), primarily referring to exosomes, have emerged as potent tools for investigating pathological mechanisms and facilitating precise diagnostics owing to their ability to transfer informative molecules between cells and their accessibility from diverse biological fluids. Despite the multitude of biomedical applications, achieving enhanced specificity and sensitivity in detecting trace sEV samples continues to pose a significant challenge. Considering the potential of electrochemical sensing in efficient molecular detection, this study proposes a viable strategy for specifically recognizing sEVs by targeting their membrane proteins. Additionally, it demonstrates sensitive and quantitative detection of sEVs based on the unique performance of PbS colloidal quantum dots (CQDs) nanomaterials. The good immobilization of target proteins on the chemically modified electrode is achieved through the synergistic effect of the charge–discharge mechanism and strong suspension bonds of PbS CQDs. The results obtained from the analysis of differential pulse voltammetry demonstrate rapid and highly sensitive electrochemical responses. The CD63 antibody-modified sensor can achieve highly sensitive detection of sEVs, providing a wide linear detection range (10 2 ∼ 10 8 particles mL −1 ) and a low detection limit (19 particles mL −1 ). The established method is ultimately employed to differentiate the sEVs originating from distinct tumor cells, thereby demonstrating its potential in membrane-biomarker-based diagnostics. Consequently, the presented electrochemical sensor demonstrates remarkable efficiency in quantifying EVs with exceptional specificity and sensitivity, thereby offering extensive prospects for applications in EV analysis and point-of-care tests.
Tumor exosomes, known as maternal cell messengers, play an important role in cancer occurrence, proliferation, metastasis, immune escape, drug resistance, and other processes and are an entry point for cancer research. However, there is still a lack of an efficient detection technology for exosomes. In this study, the ultrahigh sensitivity SERS nanoprobe with a three dimensional (3D) magnetic core/Au nanocolumn/Au nanoparticles shell strongly coupling multistage structure (Fe3O4@NR-NPs) was constructed by crystal growth of nanocrystals in the confined space of a central radiating single particle mesoporous molecular sieve channel and strong coupling secondary growth of gold particles. The exosomes were confined onto the “hot spot” of plasmonic nanoparticles and rapidly enriched by CD63 antibody functional-Fe3O4@NR-NPs to achieve high sensitivity detection, with the limit of detection of 1 × 103 particles/mL (S/N = 3). The spectral data set of different exosomes is applied to train for multivariate classification of cell types and to estimate how the normal exosome data resemble cancer cell exosomes by principal component analysis (PCA). Finally, this detection method has also been successfully employed for the detection of exosomes in complex samples; this proves that the proposed SERS-based method is a promising tool for clinical cancer screening.
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