Advances in Extracellular Vesicle-Based Surface-Enhanced Raman Spectroscopy for Cancer Diagnosis

As a noninvasive liquid biopsy approach, extracellular vesicle (EV)-based detection offers significant advantages in reflecting real-time tumor dynamis and overcoming the limitations of conventional tissue biopsy. EVs, nanoscale vesicles secreted by cells, carry diverse biomolecules such as proteins and nucleic acids, playing key roles in tumor progression, metastasis, and immune evasion, and have emerged as promising biomarkers for cancer liquid biopsy. Surface-enhanced Raman spectroscopy (SERS), characterized by high sensitivity, resistance to photobleaching, minimal sample consumption, and multiplexing capability, has shown great potential in EV analysis. This review systematically summarizes current methods for EV isolation, characterization, and storage, with a focus on label-free and label-based SERS detection strategies for early cancer diagnosis, treatment response monitoring, and prognosis evaluation. Furthermore, the integration of SERS with machine learning and deep learning algorithms has substantially improved diagnostic accuracy and cancer subtyping. Despite remaining challenges, such as optimization of SERS substrate performance, intelligent processing of Raman spectral fingerprints, and clinical translation, EV-based SERS technology holds great promise for precision oncology.