Construction of pH‐Dependent Nanozymes with Oxygen Vacancies as the High‐Efficient Reactive Oxygen Species Scavenger for Oral‐Administrated Anti‐Inflammatory Therapy

It is of great significance to eliminate excessive reactive oxygen species (ROS) for treating inflammatory bowel disease (IBD). Herein, for the first time, a novel nanozyme NiCo₂ O₄ @PVP is constructed via a step-by-step strategy. Noticeably, the existence of oxygen vacancy in the NiCo₂ O₄ @PVP is helpful for capturing oxygenated compounds, while both redox couples of Co³⁺ /Co²⁺ and Ni³⁺ /Ni²⁺ will offer richer catalytic sites. As expected, the obtained NiCo₂ O₄ @PVP exhibits pH-dependent multiple mimic enzymatic activities. Benefiting from the introduction of polyvinylpyrrolidone (PVP), the NiCo₂ O₄ @PVP possesses good physiological stability and excellent biosafety in stomach and intestines' environment. Meanwhile, the NiCo₂ O₄ @PVP also presents strong scavenging activities to ROS in vitro, including ^• O₂^- , H₂ O₂ , as well as ^• OH. Furthermore, a dextran sodium sulfate (DSS)-induced colitis model is established for evaluating the anti-inflammatory activity of NiCo₂ O₄ @PVP in vivo. Based on the size-mediated and charge-mediated mechanisms, the nanozyme can pass through the digestive tract and target the inflamed site for oral-administrated anti-inflammatory therapy. More interestingly, compared with the model group, the expression levels of inflammatory factors (e.g., Interleukin- 6 (IL-6), Interleukin- 1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS)) in colon of mice show a significant decrease after nanozyme intervention, thereby inhibiting the development of IBD. In short, current work provides an alternative therapy for patients suffering from IBD.