An AND‐Gate DNA Nanodevice for Dual Protein‐Mediated, Tumor‐Specific Imaging

Comprehensive Summary Sensitive and specific imaging of tumor‐associated biomarkers offers an effective way for cancer diagnosis. However, most of the reported imaging probes are limited to the targeting of a single biomarker, which may impair imaging precision. Here, we report an aptamer‐based, AND‐gate DNA nanodevice that relies on the sequential processing of two tumor‐associated proteins to produce a specific fluorescent signal for precise tumor imaging. The DNA nanodevice integrates an AS1411 aptamer to bind cell surface nucleolin for tumor targeting and a DNA sensor to respond to intracellular apurinic/apyrimidinic endonuclease 1 for activatable imaging. We evaluated the performance of the system in both living cells and a tumor‐bearing mouse model, and demonstrated its capability in tumor cell‐specific imaging. We anticipate that this strategy will accelerate the design of multivariate protein‐stimulated probes for tumor diagnosis.