Ligand-Dependent Activity Engineering of Glutathione Peroxidase-Mimicking MIL-47(V) Metal-Organic Framework Nanozyme for Therapy

Glutathione peroxidase (GPx) plays an important role in maintaining the reactive oxygen metabolic balance, yet limited GPx-mimicking nanozymes are currently available for in vivo therapy. Herein, a ligand engineering strategy is developed to modulate the GPx-mimicking activity of a metal-organic framework (MOF) nanozyme. With different substituted ligands, the GPx-mimicking activities of MIL-47(V)-X (MIL stands for Materials of Institute Lavoisier; X=F, Br, NH2, CH3, OH, and H) MOFs are rationally regulated. With the best one as an example, both in vitro and in vivo experiments reveal the excellent antioxidation ability of MIL-47(V)-NH2, which alleviates the inflammatory response effectively for both ear injury and colitis, and is more active than MIL-47(V). This study proves that high-performance GPx-mimicking nanozymes can be rationally designed by a ligand engineering strategy, and that structure-activity relationships can direct the in vivo therapy. This study enriches nanozyme research and expands the range of biomimetic MOFs.

Automated summary

A ligand engineering strategy was developed to modulate the GPx-mimicking activity of a metal-organic framework (MOF) nanozyme, resulting in the rational regulation of the GPx-mimicking activities of MIL-47(V)-X MOFs. Among them, MIL-47(V)-NH2 demonstrated excellent antioxidation ability, effectively alleviating inflammatory responses in both ear injury and colitis models. This study proves the feasibility of designing high-performance GPx-mimicking nanozymes and highlights the importance of structure-activity relationships in directing in vivo therapy.