Ultrasensitive detection of circulating tumor cells in clinical blood samples by a three-dimensional network nanovehicle-based aptasensor platform

Abstract

A burgeoning topic in the early diagnosis and treatment of cancer is the sensitive and precise quantification of circulating tumor cells (CTCs). However, due to the extremely low CTC concentrations in the blood, traditional enrichment and identification methods for CTCs are prone to false negative results. Here, to specifically identify and improve the sensitivity of CTC detection in the blood, we designed a novel fluorometric turn-on aptasensor platform based on a three-dimensional network nanovehicle (TDNN) modified with a PEG derivative and AS1411 aptamer specifically targeting the nucleolin protein. The limit of detection (LOD) of the aptasensor platform was as low as 2 cells per mL, which was remarkably better than that of the single nanoparticle ASS1. Notably, the novel aptasensor platform showed excellent specificity and sensitivity as well as negligible fluorescent background for quantitative and visualization detection of CTCs in peripheral blood samples without enrichment, centrifugation and washing steps. More importantly, the number of CTCs identified by TDNN was significantly higher in metastatic patients than in nonmetastatic patients, while CTCs were not detected in the blood samples of healthy donors. In conclusion, the aptasensor platform provides an available and promising tool for CTC identification and cancer metastasis prediction in clinical blood samples.