Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan.
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan.
Antioxid Redox Signal. 2022 Jan;36(1-3):70-80. doi: 10.1089/ars.2021.0103. Epub 2021 Sep 7.
Ischemia-reperfusion (IR) injury is a major component of severe damage in vascular occlusion during stroke, myocardial infarction, surgery, and organ transplantation, and is exacerbated by the excessive generation of reactive oxygen species (ROS), which occurs particularly during reperfusion. With the aging of the population, IR injury is becoming a serious problem in various organs, such as the kidney, brain, and heart, as well as in the mesenteric capillaries. To prevent reperfusion injuries, natural and synthetic low-molecular-weight (LMW) antioxidants have been well studied. However, these LMW antioxidants have various problems, including adverse effects due to excessive cellular uptake and their rapid clearance by the kidney, and cannot fully exert their potent antioxidant capacity . To overcome these problems, we designed and developed redox polymers with antioxidants covalently conjugated with them. These polymers self-assemble into nanoparticles in aqueous media, referred to as redox nanoparticles (RNPs). RNPs suppress their uptake into normal cells, accumulate at inflammation sites, and effectively scavenge ROS in damaged tissues. We had developed two types of RNPs: RNP, which disintegrates in response to acidic pH; and RNP, which does not collapse, regardless of the environmental pH. Utilizing the pH-sensitive and -insensitive characteristics of RNP and RNP, respectively, RNPs were found to exhibit remarkable therapeutic effects on various oxidative stress disorders, including IR injuries. Thus, RNPs are promising nanomedicines for use as next-generation antioxidants. This review summarizes the therapeutic impacts of RNPs in the treatment of kidney, cerebral, myocardial, and intestinal IR injuries. 36, 70-80.
缺血再灌注 (IR) 损伤是中风、心肌梗死、手术和器官移植过程中血管阻塞严重损伤的主要组成部分，并且由于活性氧 (ROS) 的过度产生而加剧，这种情况尤其在再灌注期间发生。随着人口老龄化，IR 损伤成为肾脏、大脑和心脏等各种器官以及肠系膜毛细血管中的一个严重问题。为了防止再灌注损伤，天然和合成的低分子量 (LMW) 抗氧化剂已经得到了很好的研究。然而，这些 LMW 抗氧化剂存在各种问题，包括由于细胞摄取过多和肾脏快速清除而引起的不良反应，并且不能充分发挥其强大的抗氧化能力。为了克服这些问题，我们设计并开发了将抗氧化剂共价连接到它们上的氧化还原聚合物。这些聚合物在水性介质中自组装成纳米颗粒，称为氧化还原纳米颗粒 (RNP)。RNP 抑制其被正常细胞摄取，在炎症部位积累，并有效清除受损组织中的 ROS。我们已经开发了两种类型的 RNP：RNP，其响应酸性 pH 而分解；以及 RNP，其无论环境 pH 值如何都不会崩溃。利用 RNP 和 RNP 的 pH 敏感和不敏感特性，分别发现 RNP 在各种氧化应激疾病的治疗中具有显著的治疗效果，包括 IR 损伤。因此，RNP 是作为下一代抗氧化剂有前途的纳米药物。这篇综述总结了 RNP 在治疗肾、脑、心肌和肠 IR 损伤中的治疗作用。36,70-80。
