Muscles of peripheral artery disease (PAD) patients are under oxidative stress associated with a significantly elevated level of reactive oxygen species (ROS) including hydrogen peroxide (H₂O₂). Curcumin is a major active constituent of turmeric and is well known for its highly potent antioxidant, anti-inflammatory and angiogenic effects. We previously reported antioxidant vanillyl alcohol-incorporated copolyoxalate (PVAX) which is designed to rapidly scavenge H₂O₂ and release bioactive vanillyl alcohol and CO₂ in a H₂O₂-triggered manner. In this work, we developed curcumin-loaded PVAX (CUR-PVAX) nanoparticles as contrast-enhanced ultrasound imaging agents as well as on-demand therapeutic agents for ischemic injuries based on the hypothesis that PVAX nanoparticles generate echogenic CO₂ bubbles through H₂O₂-triggered oxidation of peroxalate esters and the merger of curcumin and PVAX exerts H₂O₂-activatable synergistic therapeutic actions. CUR-PVAX nanoparticles displayed the drastic ultrasound signal in ischemic areas by generating CO₂ bubbles. CUR-PVAX nanoparticles exhibited significantly higher antioxidant and anti-inflammatory activities than empty PVAX nanoparticles and equivalent curcumin in vascular endothelial cells. A mouse model of ischemic injury was used to evaluate the potential of CUR-PVAX nanoparticles as ultrasound imaging agents and on-demand therapeutic agents. CUR-PVAX nanoparticles significantly suppressed the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Moreover, CUR-PVAX nanoparticles significantly enhanced the level of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1), leading to blood perfusion into ischemic tissues. We, therefore, believe that CUR-PVAX nanoparticles hold great translational potential as novel theranostic agents for ischemic diseases such as PAD.

周围动脉疾病（PAD）患者的肌肉处于氧化应激状态，其中包括过氧化氢（H ₂ O ₂）的活性氧（ROS）含量显着升高。姜黄素是姜黄的主要活性成分，以其高效的抗氧化剂，消炎和血管生成作用而闻名。我们以前报道抗氧化剂香草醇并入copolyoxalate（PVAX），其被设计成迅速扫ħ ₂ ö ₂和释放生物活性香草醇和CO ₂再在H ₂ ö ₂触发方式。在这项工作中，基于PVAX纳米粒子通过H ₂ O产生回声CO ₂气泡的假设，我们开发了姜黄素负载的PVAX（CUR-PVAX）纳米粒子作为造影剂增强型超声成像剂以及按需治疗药物，用于缺血性损伤过草酸酯的_2-触发氧化以及姜黄素和PVAX的合并发挥了H ₂ O ₂活化的协同治疗作用。CUR-PVAX纳米颗粒通过产生CO ₂在缺血区域显示剧烈的超声信号气泡。在血管内皮细胞中，CUR-PVAX纳米颗粒比空的PVAX纳米颗粒和等效的姜黄素具有更高的抗氧化和抗炎活性。使用小鼠缺血性损伤模型评估CUR-PVAX纳米颗粒作为超声显像剂和按需治疗剂的潜力。CUR-PVAX纳米颗粒可显着抑制促炎性细胞因子的表达，例如肿瘤坏死因子-α（TNF-α）和白介素-1β（IL-1β）。此外，CUR-PVAX纳米颗粒显着提高了血管内皮生长因子（VEGF）和血小板内皮细胞粘附分子1（PECAM-1）的水平，导致血液灌注到缺血组织中。因此，我们