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构建具有氧空位的 pH 依赖性纳米酶作为高效活性氧物种清除剂用于口服抗炎治疗。

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

机构信息

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, 300071, P. R. China.

Institute of Health Service and Transfusion Medicine, Beijing, 100850, P. R. China.

出版信息

Adv Healthc Mater. 2021 Dec;10(23):e2101618. doi: 10.1002/adhm.202101618. Epub 2021 Sep 26.

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 NiCo O @PVP is constructed via a step-by-step strategy. Noticeably, the existence of oxygen vacancy in the NiCo O @PVP is helpful for capturing oxygenated compounds, while both redox couples of Co /Co and Ni /Ni will offer richer catalytic sites. As expected, the obtained NiCo O @PVP exhibits pH-dependent multiple mimic enzymatic activities. Benefiting from the introduction of polyvinylpyrrolidone (PVP), the NiCo O @PVP possesses good physiological stability and excellent biosafety in stomach and intestines' environment. Meanwhile, the NiCo O @PVP also presents strong scavenging activities to ROS in vitro, including O , H O , as well as OH. Furthermore, a dextran sodium sulfate (DSS)-induced colitis model is established for evaluating the anti-inflammatory activity of NiCo O @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.

摘要

消除过多的活性氧(ROS)对于治疗炎症性肠病(IBD)具有重要意义。在此,我们首次通过分步策略构建了一种新型纳米酶 NiCoO@PVP。值得注意的是,NiCoO@PVP 中氧空位的存在有助于捕获含氧化合物,而 Co/Co 和 Ni/Ni 的氧化还原对将提供更丰富的催化位点。不出所料,所获得的 NiCoO@PVP 表现出 pH 依赖性的多种模拟酶活性。得益于聚乙烯吡咯烷酮(PVP)的引入,NiCoO@PVP 在胃和肠道环境中具有良好的生理稳定性和优异的生物安全性。同时,NiCoO@PVP 还在体外表现出对 ROS 的强大清除活性,包括 O 2 、H 2 O 2 和·OH。此外,建立葡聚糖硫酸钠(DSS)诱导的结肠炎模型来评估 NiCoO@PVP 在体内的抗炎活性。基于尺寸介导和电荷介导的机制,纳米酶可以穿过消化道并靶向炎症部位进行口服抗炎治疗。更有趣的是,与模型组相比,纳米酶干预后小鼠结肠中炎症因子(如白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和诱导型一氧化氮合酶(iNOS))的表达水平显著降低,从而抑制 IBD 的发展。总之,本研究为炎症性肠病患者提供了一种替代治疗方法。

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