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

Abstract

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.