Nucleolin-responsive aptamer-linked nanocarrier platform for ultrasensitive detection and imaging of circulating tumor cells in human blood

Highly sensitive quantitative detection of circulating tumor cells (CTCs) is crucial for early cancer screening and monitoring treatment. However, due to the extremely low concentration of CTCs in peripheral blood, traditional enrichment and identification protocols often yield false negatives. This study presents a novel fluorescence-activated aptamer sensing platform designed to enhance both the specificity and sensitivity of CTC detection. The platform employs polyethylene glycol-modified nanocarriers (ASA) that are surface-loaded with the AS1411 aptamer, which specifically targets nucleolin, thereby enabling precise recognition of CTCs. The detection limit of this system is as low as 2 cells/mL. Notably, this platform enables rapid, quantitative, and visual detection of CTCs in peripheral blood samples without dedicated CTC capture/enrichment, centrifugation, or washing steps, exhibiting excellent sensitivity and selectivity. Further analysis showed significantly higher CTC counts in metastatic cancer patients compared to non-metastatic patients, with no CTCs detected in healthy donor samples. Overall, this aptamer-based sensing platform provides an efficient and promising technical approach for clinical CTC detection and assessment of tumor metastasis risk.