Here, an integrated cascade nanozyme with a formulation of Pt@PCN222-Mn is developed to eliminate excessive reactive oxygen species (ROS). This nanozyme mimics superoxide dismutase by incorporation of a Mn–[5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato]–based metal-organic framework compound capable of transforming oxygen radicals to hydrogen peroxide. The second mimicked functionality is that of catalase by incorporation of Pt nanoparticles, which catalyze hydrogen peroxide disproportionation to water and oxygen. Both in vitro and in vivo experimental measurements reveal the synergistic ROS-scavenging capacity of such an integrated cascade nanozyme. Two forms of inflammatory bowel disease (IBD; i.e., ulcerative colitis and Crohn’s disease) can be effectively relieved by treatment with the cascade nanozyme. This study not only provides a new method for constructing enzyme-like cascade systems but also illustrates their efficient therapeutic promise in the treatment of in vivo IBDs.

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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, al igand engineering strategy is developed to modulate the GPx-mimicking activity of am etal-organic framework (MOF) nanozyme.W ith different substituted ligands,t he GPx-mimicking activities of MIL-47(V)-X (MIL stands for Materials of Institute Lavoisier;X= F, Br,N H 2 ,C H 3 ,O H, and H) MOFs are rationally regulated. With the best one as an example,b oth in vitro and in vivo experiments reveal the excellent antioxidation ability of MIL-47(V)-NH 2 ,w hicha lleviates the inflammatory response effectively for both ear injury and colitis,a nd is more active than MIL-47(V). This study proves that high-performance GPx-mimicking nanozymes can be rationally designed by al igand engineering strategy,a nd that structure-activity relationships can direct the in vivo therapy. This study enriches nanozyme researcha nd expands the range of biomimetic MOFs.

The repair of skeletal defects in maxillofacial region remains an intractable problem, the rising technology of bone tissue engineering provides a new strategy to solve it. Scaffolds, a crucial element of tissue engineering, must have favorable biocompatibility as well as osteoinductivity. In this study, we prepared berberine/polycaprolactone/collagen (BBR/PCL/COL) scaffolds with different concentrations of berberine (BBR) (25, 50, 75 and 100 μg/mL) through electrospinning. The influence of dosage on scaffold morphology, cell behavior and in vivo bone defect repair were systematically studied. The results indicated that scaffolds could release BBR stably for up to 27 days. Experiments in vitro showed that BBR/PCL/COL scaffolds had appropriate biocompatibility in the concentration of 25–75 μg/mL, and 50 and 75 μg/mL scaffolds could significantly promote osteogenic differentiation of dental pulp stem cells. Scaffold with 50 μg/mL BBR was implanted into the critical bone defect of rats to evaluate the ability of bone repair in vivo. It was found that BBR/PCL/COL scaffold performed more favorable than polycaprolactone/collagen (PCL/COL) scaffold. Overall, our study is the first to evaluate the capability of in vivo bone repair of BBR/PCL/COL electrospun scaffold. The results indicate that BBR/PCL/COL scaffold has prospective potential for tissue engineering applications in bone regeneration therapy.

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