Cascade-enhanced based-polyoxometalates nanozyme for glutathione detection and tumor cell disruption

Nanozymes with biological enzyme activity show great promise in biochemical analysis and medicine, yet single-activity nanozymes were limited by low catalytic efficiency and strict catalytic environment requirements. Consequently, the development of nanozymes with multiple enzyme activities presents a significant challenge. In the work, a vanadium-capped polyoxometalates (POMs)-encapsulating metal-organic framework (MOF), [Cu₁₂(Trz)₈Cl][PMo₁₂O₄₀(VO)₂], was synthesized via hydrothermal synthesis, which shows multiple enzyme activities concluding oxidase (OXD), peroxidase (POD) and catalase (CAT) activities. In the catalytic procedure, a fraction of H₂O₂ generated by the OXD is further subjected to the POD catalytic reaction and the remaining portion is transformed into O₂ through the CAT activity, in turn, supplies the driving force for the OXD-like catalytic process. This cascade reaction, in conjunction with the transformation between Cu²⁺ and Cu⁺ within the material, engenders a structure analogous to an interlocking "gear", which augments the catalytic efficacy as well as the adaptability to intricate environmental conditions of the [Cu₁₂(Trz)₈Cl][PMo₁₂O₄₀(VO)₂] enzyme. By capitalizing on this high catalytic efficiency, the rapid quantitative detection of glutathione (GSH) was established with the calculated limit of detection (LOD) 0.062 μM in the range of 5-60 μM. Surprisingly, the multi-enzymatic [Cu₁₂(Trz)₈Cl][PMo₁₂O₄₀(VO)₂] can concurrently enhance the generation of reactive oxygen species (ROS) and the depletion of GSH in the tumor microenvironment (TME), thereby inducing tumor cell apoptosis. This research holds promising application prospects in the fields of biotechnology, clinical diagnosis, and tumor therapy.