Target-Driven Cascade-Amplified Release of Loads from DNA-Gated Metal–Organic Frameworks for Electrochemical Detection of Cancer Biomarker

In this paper, a label-free and stimuli-responsive electrochemical biosensing platform was fabricated based on target-driven load release from DNA-gated metal-organic frameworks (MOFs) with cascade amplification. By using MOFs (UiO-66-NH2) as a nanocarrier of electroactive molecules (methylene blue; MB) and the programmably assembled DNA acted as the gatekeeper, the biofunctionalized MOFs (MB@DNA/MOFs) were not only used as an amplified signal label but also worked as three-dimensional tracks for biosensing. In the presence of a target, the nicking endonuclease cleavage process was triggered, leading to the generation of two strands (S1 and S2). Both S1 and S2 act as stimuli to participate in the strand displacement reaction on the MB@DNA/MOFs, which caused the unlocking of the pore to release MB, resulting in the decrease of the signal. Using carcinoembryonic antigen (CEA) as a model target, the cascade-amplified biosensor presented good performance for CEA detection, ranging from 50 fg/mL to 10 ng/mL with a detection limit of 16 fg/mL. The stimuli-responsive DNA-gated MOF-based electrochemical platform exhibited three-dimensional biosensing tracks with rational utilization of the cascade amplification, providing an effective method for cancer biomarker detection.