pH-Sensitive Dye-Based Nanobioplatform for Colorimetric Detection of Heterogeneous Circulating Tumor Cells

The efficient capture and sensitive detection of circulating tumor cells (CTCs) play a vital role in cancer diagnosis and prognosis. However, CTCs in the peripheral blood are very rare and heterogeneous, which make them difficult to isolate and detect. Herein, a novel colorimetric nanobioplatform was successfully developed for the highly efficient capture and highly sensitive detection of heterogeneous CTCs, which consisted of two parts: the multivalent aptamer-modified gold nanoparticles as the capture unit and two kinds of aptamer-functionalized pH-sensitive allochroic dyes (thymolphthalein and curcumin) @ molybdenum disulfide nanoflakes (MoS₂ NFs) acting as the visual simultaneous detection of heterogeneous CTCs. Using MCF-7 and HeLa cells as the CTC models, the capture unit can effectively isolate the CTCs due to the multivalent probe with improved affinity. The two allochroic dyes can display obvious color changes under alkaline conditions (pH 12.5) in the presence of MCF-7 and HeLa cells, which provided a rapid and sensitive strategy for visualizing simultaneous detection of heterogeneous CTCs as low as 5 cells mL^-1. This nanoplatform possessed a high sensitivity toward CTC detection owing to high dye loading capacity of MoS₂ NFs and allochroic dyes with excellent pH sensitivity. It can successfully distinguish and quantitatively detect the targeted heterogeneous CTCs from numerous interfering cells in diluted whole blood. It can also be used to detect CTCs from lysed blood samples from cancer patients, indicating promising application for cancer diagnosis.