Exosomes, as important signal transmitters, play a key role in intercellular communication, especially in cancer metastasis. There is considerable evidence that exosomes can be used as an indicator of cancer. However, convenient and sensitive methods for detecting exosomes are still technically challenging. Here, we present a convenient and highly sensitive surface-enhanced Raman scattering (SERS) based method by combining immunoaffinity, SERS nanoprobes, and portable Raman devices for specific isolation and accurate quantification of exosomes. To construct the SERS-based biosensor, the surfaces of gold nanostar@4-mercaptobenzoic acid@nanoshell structures (AuNS@4-MBA@Au) are modified with a bivalent cholesterol (B-Chol)-labeled DNA anchor to prepare SERS nanoprobes. Exosomes are specifically captured by immunomagnetic beads, and then SERS nanoprobes are fixed on the surface of exosomes by hydrophobic interactions between cholesterol and lipid membranes, thus forming a sandwich-type immunocomplex. The immunocomplex can be magnetically captured and produce enhanced SERS signals. In the absence of exosomes, the sandwich-type immunocomplex cannot be formed, and thus negligible SERS signals are detected. The degree of immunocomplex assembly and the corresponding SERS signals are positively correlated with the exosome concentration over a wide linear range of 40 to 4 × 107 particles per μL and the limit of detection is as low as 27 particles per μL. Consequently, a sensitive and simple strategy for detection of exosomes is successfully constructed. We believe that our biosensor has considerable potential as a convenient and highly sensitive quantification tool to detect exosomes in biological samples.

Simultaneous detection of cancer biomarkers holds great promise for the early diagnosis of cancer. In the present work, an ultrasensitive and reliable surface-enhanced Raman scattering (SERS) sensor has been developed for simultaneous detection of multiple liver cancer related microRNA (miRNA) biomarkers. We first proposed a novel strategy for the synthesis of nanogap-based SERS nanotags by modifying gold nanoparticles (AuNPs) with thiolated DNA and nonfluorescent small encoding molecules. We also explored a simple approach to a green synthesis of hollow silver microspheres (Ag-HMSs) with bacteria as templates. On the basis of the sandwich hybridization assay, probe DNA-conjugated SERS nanotags used as SERS nanoprobes and capture DNA-conjugated Ag-HMSs used as capture substrates were developed for the detection of target miRNA with a detection limit of 10 fM. Multiplexing capability for simultaneous detection of the three liver cancer related miRNAs with the high sensitivity and specificity was demonstrated using the proposed SERS sensor. Furthermore, the practicability of the SERS sensor was supported by the successful determination of target miRNA in cancer cells. The experimental results indicated that the proposed strategy holds significant potential for multiplex detection of cancer biomarkers and offers the opportunity for future applications in clinical diagnosis.

Exosomes are endogenous vesicles of cells, and can be used as important biomarkers for cancers.

We synthesized a novel and sensitive Au/Ag bimetallic SERS-active nanotag, Au–Ag–Ag core–shell–shell nanorod (Au@AgAgNR).

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