Spatiotemporally Controlled DNA Nanoclamps: Single-Molecule Imaging of Receptor Protein Oligomerization

Cell membrane surface receptor proteins play an important role in cellular biological processes. There are numerous methods to detect receptors, yet developing an artificially controlled and specific detection and treatment strategy remains a challenge. Herein, we develop such a strategy based on upconversion nanoparticles (UCNPs) loaded DNA probes that enable two-color ratiometric imaging excitated by a 980 nm laser. The light response controllable signal opening strategy avoids waste during probe transportation and improves sensitivity. Thereby the number of receptors on individual DU145 cell membranes is counted by single-molecule detection. Due to the different expression of specific receptor proteins, the number of single fluorescent dots counted can be used as a basis for distinguishing DU145 from other cells. This work is highly controllable to increase sensitivity, providing a platform for cancer diagnosis and treatment.