Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
Biomater Sci. 2020 Feb 21;8(4):1148-1159. doi: 10.1039/c9bm01384a. Epub 2019 Oct 30.
Biologically produced reactive oxygen species (ROS) are important signaling molecules in the human body. Despite their importance under normal conditions, abnormal overproduction of ROS under unbalanced or irregular homeostasis can cause severe inflammatory diseases. Various antioxidants have been developed in the biomedical field to resolve high levels of ROS; however, high doses of natural antioxidants such as polyphenol can induce side effects on health. Further, synthetic antioxidants are still controversial in regards to their safety and their complicated synthesis. Inspired from our previous work, a nitric oxide-scavenging nanogel designed for treating rheumatoid arthritis, we report herein a biocompatible tannic acid (TA)-based nanogel as an effective ROS scavenger. A polymeric phenylboronic acid-tannic acid nanogel (PTNG) was prepared by simply mixing through to the formation of phenylboronic ester bonds between polymeric phenylboronate and TA. We focused on the reaction of phenylboronic ester with HO, which readily consumes HO molecules, and applied it as an antioxidant. In addition, TA is a well-known antioxidant, specifically a free radical scavenger; thus, we expected combinatory ROS scavenging effects for PTNG. Various ROS scavenging assays revealed the significant antioxidant effects of PTNG. Under an induced inflammation model in vitro, our PTNG showed high biocompatibility as well as strong anti-inflammatory effects. Furthermore, in the zymosan-induced peritonitis mouse model, a representative acute inflammation model in vivo, PTNG reduced significant neutrophil recruitment and pro-inflammatory cytokines, indicating successful alleviation of inflammation. On the basis of these results, we suggest that PTNG has great potential as an antioxidant and should find application in the treatment of further ROS-overproducing inflammatory diseases.
生物产生的活性氧（ROS）是人体内重要的信号分子。尽管在正常情况下它们很重要，但在失衡或不规则的内环境下，ROS 的异常过度产生会导致严重的炎症性疾病。在生物医学领域已经开发出各种抗氧化剂来解决高水平的 ROS 问题；然而，高剂量的天然抗氧化剂，如多酚，可能会对健康产生副作用。此外，合成抗氧化剂的安全性及其复杂的合成仍然存在争议。受我们之前治疗类风湿性关节炎的一氧化氮清除纳米凝胶的启发，我们在此报告了一种基于单宁酸（TA）的生物相容性纳米凝胶，它是一种有效的 ROS 清除剂。通过简单地混合，形成聚合物苯硼酸和 TA 之间的苯硼酸酯键，制备了聚合物苯硼酸-单宁酸纳米凝胶（PTNG）。我们专注于苯硼酸酯与 HO 的反应，HO 容易消耗 HO 分子，并将其应用于抗氧化剂。此外，TA 是一种众所周知的抗氧化剂，特别是自由基清除剂；因此，我们期望 PTNG 具有组合的 ROS 清除效果。各种 ROS 清除实验表明，PTNG 具有显著的抗氧化效果。在体外诱导炎症模型中，我们的 PTNG 表现出高生物相容性和强大的抗炎作用。此外，在酵母聚糖诱导的腹膜炎小鼠模型（体内代表性的急性炎症模型）中，PTNG 减少了显著的中性粒细胞募集和促炎细胞因子，表明炎症得到了成功缓解。基于这些结果，我们认为 PTNG 作为抗氧化剂具有很大的潜力，应该在治疗进一步产生过多 ROS 的炎症性疾病方面得到应用。
