Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury.
Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury.
复制标题
DOI：
10.1016/j.jconrel.2013.09.020
复制
发表时间：
2013-12-28
期刊：
影响因子：
--
通讯作者：
Kang PM
中科院分区：
文献类型：
--
作者：
Lee D;Bae S;Ke Q;Lee J;Song B;Karumanchi SA;Khang G;Choi HS;Kang PM
高水平过氧化氢（H2 O2）的产生是缺血/再灌注（I/R）损伤发病机制中的罪魁祸首。在这项研究中，我们报告了一种新的诊断和治疗策略的I/R损伤的基础上H2 O2活化的共聚草酸酯纳米粒子使用小鼠模型的后肢I/R损伤。该纳米颗粒由羟基苯甲醇（HBA）结合共聚草酸酯（HPOX），在过氧化氢的存在下，完全降解成三个已知的和安全的化合物，环己烷二甲醇，HBA和CO2。HPOX以剂量依赖性方式有效地清除H2 O2，并水解以释放HBA，其在体外和体内后肢I/R模型中都发挥固有的抗氧化和抗炎活性。HPOX纳米粒子负载荧光团有效和强大的图像H2 O2产生的后肢I/R损伤，证明了它们的生物成像H2 O2相关疾病的潜力。此外，负载有抗凋亡药物的HPOX纳米颗粒在I/R损伤后有效地释放药物有效载荷，表现出它们对于I/R损伤的靶向药物递送系统的有效性。我们预计，多功能HPOX纳米粒子作为H2 O2显像剂，治疗和药物输送系统的H2 O2相关疾病有很大的潜力。
The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the generation of high level of hydrogen peroxide (H2O2). In this study, we report a novel diagnostic and therapeutic strategy for I/R injury based on H2O2-activatable copolyoxalate nanoparticles using a murine model of hind limb I/R injury. The nanoparticles are composed of hydroxybenzyl alcohol (HBA)-incorporating copolyoxalate (HPOX) that, in the presence of H2O2, degrades completely into three known and safe compounds, cyclohexanedimethanol, HBA and CO2. HPOX effectively scavenges H2O2 in a dose-dependent manner and hydrolyzes to release HBA which exerts intrinsic antioxidant and anti-inflammatory activities both in vitro and in vivo models of hind limb I/R. HPOX nanoparticles loaded with fluorophore effectively and robustly image H2O2 generated in hind limb I/R injury, demonstrating their potential for bioimaging of H2O2-associated diseases. Furthermore, HPOX nanoparticles loaded with anti-apoptotic drug effectively release the drug payload after I/R injury, exhibiting their effectiveness for a targeted drug delivery system for I/R injury. We anticipate that multifunctional HPOX nanoparticles have great potential as H2O2 imaging agents, therapeutics and drug delivery systems for H2O2-associated diseases.
登录
查看更多内容
影响因子：
19.6
作者：
Aragno, M;Cutrin, JC;Boccuzzi, G
通讯作者：
Boccuzzi, G
影响因子：
15.9
作者：
GOTTLIEB, RA;BURLESON, KO;ENGLER, RL
通讯作者：
ENGLER, RL
影响因子：
4.1
作者：
Lee, Yujung;Kwon, Jeongil;Lee, Dongwon
通讯作者：
Lee, Dongwon
DOI：
10.1016/s0967-2109(02)00070-4
发表时间：
2002-12-01
期刊：
CARDIOVASCULAR SURGERY
影响因子：
--
作者：
Blaisdell, FW
通讯作者：
Blaisdell, FW
影响因子：
6.2
作者：
Park, Hyunjin;Kim, Soojin;Lee, Dongwon
通讯作者：
Lee, Dongwon