HCl-Protonated Metal–Organic Framework-Confined Au Nanoclusters with Enhanced Catalytic Activity and Specificity for Anti-interference Biosensing

Development of nanozymes with enhanced activity and specificity can be profitable for sensitive and anti-interference biosensing. Herein, we developed a protonation strategy to fabricate metal-organic framework-confined Au nanoclusters with enhanced catalytic activity and specificity. Organic acid acetic acid (HAc), tannins (TA), and inorganic acid hydrochloric acid (HCl) were used to etch the UiO-66-NH₂ skeleton, and only HCl can introduce reasonable protonation on UiO-66-NH₂ without structural damage. The peroxidase (POD)- and glucose oxidase-mimic catalytic activities of UiO-66-NH₂@Au can be improved simultaneously. Mechanism study revealed that the surface protonation can regulate the charge density and binding energy of the Au nanocluster growth on the surface of UiO-66-NH₂, resulting in an improved catalytic activity to H₂O₂ and glucose molecules simultaneously. Interestingly, the oxidase-mimic activity of protonated UiO-66-NH₂@Au was absolutely suppressed; thus, the POD-specific catalytic activity can be used as anti-interference colorimetric tags in colorectal cancer (CRC) biomarker biosensing. Combined with the lateral flow assay, a detection limit of 17 pg/mL for carcinoembryonic antigen (CEA) and 0.11 U/mL for carbohydrate antigen 19-9 (CA19-9) can be visually detected simultaneously within 15 min. For clinical diagnosis, CRC patients can be differentiated from healthy controls with better accuracy than by using commercial ELISA kits. Moreover, protonated UiO-66-NH₂@Au can specifically catalyze glucose and did not respond to the glucose analogues and can hence be directly used for salivary glucose detection. In addition, we found that HCl-protonated UiO-66-NH₂ can be a universal method to improve the POD-mimic catalytic activity of UiO-66-NH₂ confined with other catalytic metals such as Pt, Ru, and Pd. It highlights that HCl-protonated nanozymes can be a simple strategy to fabricate UiO-66-NH₂ confined nanozymes with enhanced catalytic activity and specificity.