Screening and multiple detection of cancer exosomes using an SERS-based method

Abstract

As a kind of most important cancer biomarker, exosomes are getting more frequently investigated in cancer diagnosis. In this study, we proposed an SERS-based method for the screening and simultaneous multiple detection of exosomes using magnetic substrates and SERS probes. Specifically, the capturing substrates are achieved using gold shell magnetic nanobeads modified by aptamers, which can capture most kinds of exosomes by recognizing the generic surface protein CD63. Moreover, the SERS probes are made of gold nanoparticles decorated with a Raman reporter and a specific aptamer for targeting exosomes. Further, for the simultaneous detection of multiple kinds of exosomes, three kinds of SERS probes were designed using different SERS reporters. While detecting specific kinds of exosomes, the capturing substrates were mixed with these three kinds of SERS probes. When the target exosome is present, an apta-immunocomplex can be formed among the target exosomes, the substrate, and the corresponding kind of SERS probes, and the other non-specific SERS probes remain in the suspension. Hence, an SERS signal with a decreased intensity will be detected in the supernatant, indicating the presence of the target exosomes. Finally, this detection method has also been successfully employed for the detection of exosomes in real blood samples; this proves that the proposed SERS-based method is a promising tool for clinical cancer screening based on exosomes.

Cancer Diagnosis through SERS and Other Related Techniques

“…The improvement provided by Wang et al consists in including magnetic properties along with the plasmonic ones, facilitating the process of separation of the analyte from the whole sample. They developed a method based on an exosomal capturing probe based on a gold shell magnetic nanostructure with antibodies against surface protein CD63 and a detecting probe consisting in AuNPs functionalized with aptamers/Raman probes (Aptamer H2/DTNB, aptamer CEA/MMC, and aptamer PSMA/2NAT), for breast cancer, colorectal cancer, and prostate cancer, respectively [41]. After adding a known concentration of capturing and detection probes to blood samples, the immunocomplex takes place, and magnetic beads are collected with a magnet.…”

Sensing of circulating cancer biomarkers with metal nanoparticles

“…The magnetic properties of magnetic nanobeads covered by a Au shell have been exploited for both exosome separation and particle aggregation (to generate hot spots) during SERS detection. 344 If the exosomes were dried prior to analysis, additional SERS peaks developed as a consequence of the rupture of the vesicle membranes, exposing the internal content of the exosome. 345 Alternatively, different types of assays have targeted surface antigens to quantify and characterize exosomes, since surface proteins are fundamental for the vesicle biological functions and can provide tumor fingerprints.…”

Advanced Functional Structure‐Based Sensing and Imaging Strategies for Cancer Detection: Possibilities, Opportunities, Challenges, and Prospects

“…The label free detection capability of the SERS approach provided highly selective and multiplexed quantification of exosomes with desirable efficiency. In this context, the feasibility of the SERS‐based immunoassay for multiplexed detection of cancer specific exosomes was reported recently . Specifically, three different SERS nanoprobes were prepared by combining Au NPs with aptamer H2, aptamer CEA, and aptamer PSMA ( Figure ).…”

“…The multiplex capability in the aptaimmunocomplex is generated by using specific aptamers, which specifically bind to three different kinds of RMs (5,5′‐dithiobis(2‐nitrobenzoic acid), 7‐mercapto‐4‐methylcoumarin (MMC), and 2‐naphthalenethiol). Reproduced with permission . Copyright 2018, The Royal Society of Chemistry.…”