Light up multiple protein dimers on cell surface based on proximity-induced fluorescence activation of DNA-templated sliver nanoclusters

Efficient and multiple analysis of receptor protein dimers is highly necessary, due to their important role in the occurrence and development of cancer. Herein, we report a turn-on strategy to visualize human epidermal growth factor receptor (HER) dimers on cell surfaces. By taking advantages of specific aptamer recognition and proximity-induced fluorescence activation of DNA-templated sliver nanoclusters (DNA/AgNCs) by guanine (G)-rich sequence, we attached the two kind of DNA/AgNCs sequence with different fluorescence properties to the corresponding HER aptamer to form aptamer-functionalized AgNCs probes, and attached G-rich sequence to the corresponding HER aptamer as enhancer. In the presence of protein dimers, after aptamer specific recognition and binding, it will draw the dark AgNCs probes close to the G-rich probes and then excite corresponding fluorescence. As a result, this approach has successfully realized imaging of HER2:HER2 homodimer and HER2:HER3 heterodimer at the same time, which was provided a new idea for the simultaneous detection of multiple HER2 dimers in situ. This AgNCs-based light up strategy provides a potential tool for further investigation of protein dimerization on cell surface, which is more conducive to the mechanism research, accurate classification and treatment of cancer.