Functional Immunoaffinity 3D Magnetic Core–Shell Nanometallic Structure for High-Efficiency Separation and Label-Free SERS Detection of Exosomes

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.