Despite the great potential of numerous antioxidants for pharmacotherapy of diseases associated with inflammation and oxidative stress, many challenges remain for their clinical translation. Herein, a superoxidase dismutase/catalase‐mimetic material based on Tempol and phenylboronic acid pinacol ester simultaneously conjugated β‐cyclodextrin (abbreviated as TPCD), which is capable of eliminating a broad spectrum of reactive oxygen species (ROS), is reported. TPCD can be easily synthesized by sequentially conjugating two functional moieties onto a β‐cyclodextrin scaffold. The thus developed pharmacologically active material may be easily produced into antioxidant and anti‐inflammatory nanoparticles, with tunable size. TPCD nanoparticles (TPCD NP) effectively protect macrophages from oxidative stress‐induced apoptosis in vitro. Consistently, TPCD NP shows superior efficacies in three murine models of inflammatory diseases, with respect to attenuating inflammatory responses and mitigating oxidative stress. TPCD NP can also protect mice from drug‐induced organ toxicity. Besides the passive targeting effect, the broad spectrum ROS‐scavenging capability contributes to the therapeutic benefits of TPCD NP. Importantly, in vitro and in vivo preliminary experiments demonstrate the good safety profile of TPCD NP. Consequently, TPCD in its native and nanoparticle forms can be further developed as efficacious and safe therapies for treatment of inflammation and oxidative stress‐associated diseases.

中文翻译：

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用于预防炎症和药物引起的器官毒性的广谱 ROS 消除材料

尽管多种抗氧化剂在炎症和氧化应激相关疾病的药物治疗方面具有巨大潜力，但其临床转化仍面临许多挑战。在此，报道了一种基于 Tempol 和苯硼酸频哪醇酯同时缀合的 β-环糊精（缩写为 TPCD）的超氧化物酶歧化酶/过氧化氢酶模拟材料，能够消除广谱的活性氧（ROS）。通过将两个功能部分依次缀合到 β-环糊精支架上，可以轻松合成 TPCD。由此开发的药理活性材料可以很容易地生产成尺寸可调的抗氧化和抗炎纳米颗粒。TPCD 纳米粒子（TPCD NP）在体外有效保护巨噬细胞免受氧化应激诱导的细胞凋亡。一致地，TPCD NP 在三种炎症性疾病小鼠模型中显示出在减弱炎症反应和减轻氧化应激方面的卓越功效。TPCD NP 还可以保护小鼠免受药物引起的器官毒性。除了被动靶向作用外，广谱 ROS 清除能力也有助于 TPCD NP 的治疗效果。重要的是，体外和体内初步实验表明 TPCD NP 具有良好的安全性。因此，天然形式和纳米颗粒形式的 TPCD 可以进一步开发为治疗炎症和氧化应激相关疾病的有效且安全的疗法。