Quantum Dot Based Fluorescent Traffic Light Nanoprobe for Specific Imaging of Avidin-Type Biotin Receptor and Differentiation of Cancer Cells.

Sensitive and specific visualization of cell surface biotin receptors (BRs) a class of clinically important biomarkers, remains a challenge. In this work, a dual-emission ratiometric fluorescent nanoprobe is developed for specific imaging of cell surface avidin, a subtype of BRs. The nanoprobe comprises a dual-emission quantum dot nanohybrid, wherein a silica-encapsulated red-emitting QD (rQD@SiO2) is used as the "core" and green-emitting QDs (gQDs) are used as "satellites", which are further decorated with a new "love-hate"-type BR ligand, a phenanthroline-biotin conjugate with an amino linker. The nanoprobe shows intense rQD emission but quenched gQD emission by the BR ligand. Upon imaging, the rQD emission stays constant and the gQD emission is restored as cell surface avidin accrues. Accordingly, the overlaid fluorescence color collected from red and green emission changes from red to yellow and then to green. We refer to such a color change as a traffic light pattern and the nanoprobe as a fluorescent traffic light nanoprobe. We demonstrate the application of our fluorescent traffic light nanoprobe to characterize cancer cells. By the traffic light pattern, cervical carcinoma and normal cells, as well as different-type cancer cells including BR-negative colon cancer cells, BR-positive hepatoma carcinoma cells, breast cancer cells, and their subtypes, have been visually differentiated. We further demonstrate a use of our nanoprobe to distinguish the G2 phase from other stages in a cell cycle. These applications provide new insights into visualizing cell surface biomarkers with remarkable imaging resolution and accuracy.