Dual-Mode Colorimetric and Fluorescent Detection of Tumor Cells Based on Gold Nanoparticles-Loaded Phosphine Covalent Organic Frameworks

Circulating tumor cells (CTCs) are important markers for cancer. The part of tumor cells that are detached from the primary tumor or metastatic tumor and enter the blood circulation is called CTCs. It is crucial to develop a rapid, accurate, and easy-to-implement diagnostic system for CTCs for early tumor diagnosis and for monitoring progression of the disease. In this work, we reported a colorimetric and fluorescent dual-mode assay for the detection of CTCs. Our assay used magnetic nanoparticles and aptamer for CTCs capture and gold nanoparticles-loaded covalent organic frameworks (Au@COFs) for signal amplification, respectively. The magnetic nanoparticles were modified with folic acid to capture CTCs by interaction between folic acid and the folate receptor overexpressed on the surface of tumor cells. The covalent organic frameworks were engineered to have both nitro-reductase-like and glucose-oxidase-like activities. The nitro-reductase-like activity converted the substrate p-nitrophenol to p-nitroaniline for colorimetric detection, and the glucose-oxidase-like activity enabled fluorescence detection. Specifically, Au@COFs catalyzed glucose oxidation and generated hydrogen peroxide to oxidize Fe2+ to Fe3+, which converted MIL(Al)-MOF to MIL(Fe)-MOF through ion exchange, resulting in the fluorescence quenching of MIL(Al)-MOF. Our assay showed high sensitivity with a detection limit of 17 cells/mL using MCF-7 cells as model cancer cells. This work provided an efficient and ultrasensitive strategy for CTCs detection and has potential applications in cancer identification and diagnosis. Dual-mode detection system, combining colorimetric and fluorescent signals, integration of magnetic nanoparticles and aptamers for CTC capture, and utilization of covalent organic frameworks loaded with gold nanoparticles for signal amplification can improve sensitivity and accuracy.