Kang Changsun, Cho Wooram, Park Minhyung, Kim Jinsub, Park Sanghoon, Shin Dongho, Song Chulgyu, Lee Dongwon
Department of BIN Convergence Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 561-756, Republic of Korea.
Department of Electronics Engineering, Baekjedaero 567, Jeonju, Chonbuk 561-756, Republic of Korea.
Biomaterials. 2016 Apr;85:195-203. doi: 10.1016/j.biomaterials.2016.01.070. Epub 2016 Feb 2.
Overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) leads to oxidative stress, causing inflammation and cellular damages and death. H2O2 is one of the most stable and abundant ROS and H2O2-mediated oxidative stress is considered as a key mediator of cellular and tissue damages during ischemia/reperfusion (I/R) injury. Therefore, H2O2 could hold tremendous potential as a diagnostic biomarker and therapeutic target for oxidative stress-associated inflammatory conditions such as I/R injury. Here, we report a novel nanotheranostic agent that can express ultrasound imaging and simultaneous therapeutic effects for hepatic I/R treatment, which is based on H2O2-triggered CO2-generating antioxidant poly(vanillin oxalate) (PVO). PVO nanoparticles generate CO2 through H2O2-triggered oxidation of peroxalate esters and release vanillin, which exerts antioxidant and anti-inflammatory activities. PVO nanoparticles intravenously administrated remarkably enhanced the ultrasound signal in the site of hepatic I/R injury and also effectively suppressed the liver damages by inhibiting inflammation and apoptosis. To our best understanding, H2O2-responsive PVO is the first platform which generates bubbles to serve as ultrasound contrast agents and also exerts therapeutic activities. We therefore anticipate that H2O2-triggered bubble-generating antioxidant PVO nanoparticles have great potential for ultrasound imaging and therapy of H2O2-associated diseases.
过氧化氢（H2O2）等活性氧（ROS）的过度产生会导致氧化应激，引发炎症、细胞损伤和死亡。H2O2是最稳定且含量丰富的ROS之一，H2O2介导的氧化应激被认为是缺血/再灌注（I/R）损伤期间细胞和组织损伤的关键介质。因此，H2O2作为氧化应激相关炎症性疾病（如I/R损伤）的诊断生物标志物和治疗靶点具有巨大潜力。在此，我们报道了一种新型的纳米诊疗剂，它基于H2O2触发的产二氧化碳抗氧化剂聚（香草酸草酸酯）（PVO），可对肝脏I/R治疗发挥超声成像和同步治疗作用。PVO纳米颗粒通过H2O2触发的草酸酯氧化产生CO2并释放香草醛，香草醛具有抗氧化和抗炎活性。静脉注射PVO纳米颗粒可显著增强肝脏I/R损伤部位的超声信号，并通过抑制炎症和细胞凋亡有效减轻肝脏损伤。据我们所知，H2O2响应性PVO是首个既能产生气泡作为超声造影剂又能发挥治疗作用的平台。因此，我们预计H2O2触发的产气泡抗氧化剂PVO纳米颗粒在H2O2相关疾病的超声成像和治疗方面具有巨大潜力。
