Capture, Detection, and Simultaneous Identification of Rare Circulating Tumor Cells Based on a Rhodamine 6G-Loaded Metal–Organic Framework

Circulating tumor cells (CTCs) play a key role in the development of tumor metastasis. It will be a big step forward for CTC application as a reliable clinical liquid biopsy marker to be able to identify the captured CTCs while achieving a high capture efficiency within one analytical system. Herein, in this work, a stimuli-responsive and rhodamine 6G (Rho 6G)-entrapped fluorescent metal–organic framework (MOF) probe, named MOF-Rho 6G-DNA, was designed to capture, detect, and subsequently identify CTCs from blood samples of cancer patients. The probe was fabricated by modifying the epithelial cell adhesion molecule (EpCAM) hairpin DNA aptamer with Rho 6G enclosed and an Arm-DNA-attached UiO-66-NH2 MOF by sequence complementation. CTCs could be captured by the EpCAM hairpin DNA on the probe; as a result, Rho 6G loaded in the probe was released, and the number of CTCs was positively related to the concentration of released Rho 6G. An excellent correlation of fluorescence intensities with CTC numbers was obtained from 2 to 500 cells/mL. More importantly, the MOF-Rho 6G-DNA probe simultaneously realized rapid identification of the captured cells within 30 min by only relying on the residue Rho 6G in the MOF cavity. The captured target cells can be conveniently released from the probe using the complementary DNA sequence. These performance features of the probe were further verified by blood samples from patients of various types of tumor.