Tumor-derived exosomes (tExos) are highly promising biomarkers for the early diagnosis of pancreatic cancer (PC), but current detection methods are limited by complicated procedures, high sample consumption, and interference from complex matrices. In this study, we developed an immunomagnetic-MXene dual-functional probe and combined it with terahertz (THz) metamaterials to enhance the sensitivity and specificity of detecting pancreatic cancer-derived tExos. We conjugated antibodies against ZIP4 and glypican-1 (GPC-1) to magnetic beads (MBs) and MXene nanosheets, respectively, creating two probes that can simultaneously target pancreatic cancer-derived tExos, achieving highly specific sandwich-type capture of target exosomes. Moreover, MXene enhanced the THz metamaterial resonance induced by tExos and outperformed gold nanoparticles (AuNPs) in signal amplification, bringing the detection limit (LOD) down to 647 particles/mL. Our THz metamaterial sensor was able to accurately detect early tumor formation in pancreatic cancer mouse models and evaluate treatment responses. In a clinical cohort of 60 participants, the sensor distinguished pancreatic cancer patients at all stages from healthy controls with an area under the curve (AUC) of 0.997. Compared with the conventional CA19-9 test, our THz metamaterial sensor showed higher diagnostic accuracy in 11 early-stage pancreatic cancer patients (AUC: 0.991 vs. 0.809), and it also offers advantages such as simplified operation, extremely low sample requirement (10 µL), and low cost (< $5), highlighting its huge potential for clinical translation in early pancreatic cancer diagnosis.

References:

DOI:10.1002/advs.78093

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