Abstract
Exosomes have emerged as potential biomarkers for pancreatic cancer (PaC). However, it is still challenging to get quantitative detection of exosomes with the specific surface receptors. In this study, a highly sensitive detection system is first constructed for the direct quantitation of specific exosomes in real samples using hierarchical surface-enhanced Raman scattering substrate (H-SERS substrate) and rapid enrichment strategy magnetic beads @ exosomes @ SERS detection probes (MEDP). It is found that the detection system (MEDP @ H-SERS substrate) could provide a 3.5 times higher SERS intensity compared with MEDP sandwich immunocomplex only. Moreover, LRG1-positive exosomes (LRG1-Exos) and GPC1-positive exosomes (GPC1-Exos) are chosen to distinguish PaC through exosome proteomics and database screening. The lower limit of detection (LOD) is 15 particles µL-1 using the MEDP @ H-SERS substrate. Significantly, the detection in clinical samples shows that the innovative combination of LRG1-Exos and GPC1-Exos could improve the diagnostic efficiency of PaC, with an area under the operating characteristic curve (AUC) of 0.95. Even for the early-stage PaC, the diagnostic accuracy is still high (AUC = 0.95). Collectively, the findings indicate that the MEDP @ H-SERS substrate has great potential for the early diagnosis of PaC.