Aptamer-Modified Nanostructured Particles Exhibiting Sensitive Cell-Scale FRET Enable Precise Pancreatic Cancer Diagnosis

Diagnosis of pancreatic cancer (PC) at early stage remains a challenge due to the limited sensitivity and specificity of current biomarkers. Here, we develop nanostructured magnetic particles (NMPs) exhibiting highly sensitive and specific circulating tumor cells (CTCs) quantification enabled by Förster resonance energy transfer (FRET), and demonstrate precise diagnosis of PC from benign pancreatic tumors (BPT) and healthy donors (HD). The NMPs are modified with aptamer, which can preferably bind to cells with higher specificity and guarantee effective substitution of acceptors. Compared with smooth magnetic particles (SMPs), NMPs provide more binding sites for CTCs, which significantly enhances the fluorescent signal and detection limit. An ultralow detection limit (1 cell/mL) is achieved using this unique capture and detection platform. Clinical validation demonstrates the superior diagnostic performance of this CTCs-based approach, with 91.7% sensitivity in detecting PC patients and 96.6% specificity. Receiver operating characteristic (ROC) analysis reveals an area under the curve (AUC) of 0.957, outperforming conventional biomarkers (CA19-9:0.905; CEA: 0.747; CA125:0.625). Our strategy represents an important methodological progress for tumor liquid biopsy, showing promise for clinical diagnosis, monitoring, and evaluation.