Multivalent Aptamer Functionalized Ag₂S Nanodots/Hybrid Cell Membrane-Coated Magnetic Nanobioprobe for the Ultrasensitive Isolation and Detection of Circulating Tumor Cells

Circulating tumor cells (CTCs) play key roles in the development of tumor metastasis. It remains a significant challenge to capture and detect CTCs with high purity and sensitivity from blood samples. Herein, a nanoplatform is developed for the efficient isolation and ultrasensitive detection of CTCs by combining near-infrared (NIR) multivalent aptamer functionalized Ag₂S nanodots with hybrid cell membrane-coated magnetic nanoparticles. Multivalent aptamer functionalized Ag₂S nanodots are synthesized using a one-pot method under mild conditions (60 °C). White blood cell and tumor cell membranes are fused as the hybrid membrane and coated with magnetic nanoparticles, which are further modified with streptavidin (SA). Through the specific interaction of SA-biotin, the multivalent aptamer-Ag₂S nanodots are grafted with hybrid cell membrane-magnetic nanoparticles. Due to the features of hybrid cell membrane modification, multivalent aptamer functionalization, magnetic separation, and NIR fluorescence measurements, the nanoplatform shows sensitive recognition, efficient capture, easy isolation, and sensitive detection of CTCs due to its great enhancement in anti-interference from background and improvement on binding ability toward CTCs. The capture efficiency and purity for CTCs is as high as 97.63% and 96.96%, respectively. Furthermore, the nanoplatform is successfully applied to the detection of CTCs in blood samples.