ZIF-67 as a Template Generating and Tuning “Raisin Pudding”-Type Nanozymes with Multiple Enzyme-like Activities: Toward Online Electrochemical Detection of 3,4-Dihydroxyphenylacetic Acid in Living Brains

Due to its unique structure and high porosity, metal–organic frameworks (MOFs) can act not only as nanozyme materials but also as carriers to encapsulate natural enzymes and thus have received extensive attention in recent years. However, a few research studies have been conducted to investigate MOF as a template to generate and tune nanozymes in the structure and performance. In this work, the "raisin pudding"-type ZIF-67/Cu0.76Co2.24O4 nanospheres (ZIF-67/Cu0.76Co2.24O4 NSs) were obtained by rationally regulating the weight ratio of ZIF-67 and Cu(NO3)2 in the synthesis process. Here, ZIF-67 not only acts as a template but also provides a cobalt source for the synthesis of cobalt copper oxide on the surface of ZIF-67/Cu0.76Co2.24O4 NSs with multiple enzyme-like activities. The ZIF-67/Cu0.76Co2.24O4 NSs can mimic four kinds of enzymes with peroxidase-like, glutathione peroxidase-like, superoxide dismutase-like, and laccase-like activities. Based on its laccase-like activity, an online electrochemical system for continuous monitoring of 3,4-dihydroxyphenylacetic acid with good linearity in the range of 0.5–20 μM and a detection limit of 0.15 μM was established. Furthermore, the alteration of DOPAC in the brain microdialysate before and after ischemia of the rats' brain was also successfully recorded. This work not only raises a new idea for the synthesis of nanozyme materials with multiple enzyme activities but also provides a new solution for the detection of neurotransmitters in living brains.