Exosome detection via surface-enhanced Raman spectroscopy for cancer diagnosis

As nanoscale extracellular vesicles, exosomes are secreted by various cell types, and they are widely distributed in multiple biological fluids. Studies have shown that tumor-derived exosomes can carry a variety of primary tumor-specific molecules, which may represent a novel tool for the early detection of cancer. However, the clinical translation of exosomes remains a challenge due to the requirement of large quantities of samples when enriching the cancer-related exosomes in biological fluids, the insufficiency of traditional techniques for exosome subpopulations, and the complex exosome isolation of the current commercially available exosome phenotype profiling approaches. The evolving surface-enhanced Raman scattering (SERS) technology, with properties of unique optoelectronics, easy functionalization, and the particular interaction between light and nanoscale metallic materials, can achieve sensitive detection of exosomes without large quantities of samples and multiplexed phenotype profiling, providing a new mode of real-time and noninvasive analysis for cancer patients. In the present review, we mainly discussed exosome detection based on SERS, especially SERS immunoassay. The basic structure and function of exosomes were firstly introduced. Then, recent studies using the SERS technique for cancer detection were critically reviewed, which mainly included various SERS substrates, biological modification of SERS substrates, SERS-based exosome detection, and the combination of SERS and other technologies for cancer diagnosis. This review systematically discussed the essential aspects, limitations, and considerations of applying SERS technology in the detection and analysis of cancer-derived exosomes, which could provide a valuable reference for the early diagnosis of cancer through SERS technology. STATEMENT OF SIGNIFICANCE: Surface-enhanced Raman scattering (SERS) has been applied to exosomes detection to obtain better diagnostic results. In past three years, several reviews have been published in exosome detection, which were narrowly focus on methods of exosome detection. Selection and surface functionalization of the substrate and the combination detection with different methods based on SERS will provide new strategies for the detection of exosomes. This review will focus on the above aspects. This emerging detection method is constantly evolving and contributing to the early discovery of diseases in the future.