An Engineered Core–Satellite Magnetic Aptasensor with Built-In Calibration and Regeneration for Accurate Quantification of Oral Cancer Exosomes

Exosomes carry diverse biologically active substances that can be transferred between cells, thereby influencing physiological and pathological states of the organism. Abnormal exosome levels are closely associated with cancer. Consequently, the precise detection of exosomes holds considerable importance for noninvasive cancer diagnosis and monitoring. Nevertheless, achieving highly sensitive and consistently reproducible detection of exosomes continues to pose a significant challenge in clinical diagnostics. In this research, we developed a reusable magnetic aptamer-based surface-enhanced Raman scattering (SERS) sensor with built-in calibration for the accurate quantification of exosomes derived from oral cancer. The sensor was synthesized through a layer-by-layer assembly strategy to form an internal standard encoded core–satellite structure (NiFe 2 O 4 @PB@Ag), which was subsequently conjugated with SH-modified complementary DNA (cDNA) to form NiFe 2 O 4 @PB@Ag-cDNA. This was then hybridized with ROX-labeled aptamers (ROX: 6-carboxy-X-rhodamine) to construct the final NiFe 2 O 4 @PB@Ag-dsDNA SERS aptasensor. Magnetic-induced assembly of the sensor, combined with the surface plasmon effect, significantly improved the SERS performance, enabling dual amplification of both internal standard and target signals. This resulted in a 1.9-fold increase in signal intensity compared to the condition lacking magnetic-induced assembly. Furthermore, this SERS sensor exhibited a wide linear range for exosome detection, spanning from 5.0 × 10 3 to 5.0 × 10 11 particles/mL, with a limit of detection (LOD) as low as 1.15 × 10 3 particles/mL. Finally, in clinical testing of plasma samples, the sensor reliably differentiated exosome concentrations between individuals with oral cancer and healthy controls, providing a robust and reliable platform for exosome-based liquid biopsy in clinical applications.