Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea; Department of Polymer Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk 561-756, South Korea.
J Control Release. 2013 Dec 28;172(3):1102-10. doi: 10.1016/j.jconrel.2013.09.020. Epub 2013 Oct 2.
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.
在缺血/再灌注（I/R）损伤的发病机制中，主要罪魁祸首是过氧化氢（H2O2）的产生。在这项研究中，我们基于 H2O2 激活的共缩醛纳米粒子，在一种后肢 I/R 损伤的小鼠模型中，报告了一种新的 I/R 损伤的诊断和治疗策略。这些纳米粒子由包含羟基苯甲醇（HBA）的共缩醛（HPOX）组成，在 H2O2 的存在下，完全降解为三种已知的安全化合物：环己烷二甲醇、HBA 和 CO2。HPOX 以剂量依赖的方式有效清除 H2O2，并水解释放 HBA，它在体外和体内后肢 I/R 模型中都具有内在的抗氧化和抗炎活性。负载荧光团的 HPOX 纳米粒子有效地、强烈地对后肢 I/R 损伤中产生的 H2O2 进行成像，证明了它们在与 H2O2 相关疾病的生物成像中的潜力。此外，负载抗凋亡药物的 HPOX 纳米粒子在 I/R 损伤后有效释放药物有效负载，表现出它们在针对 I/R 损伤的靶向药物输送系统中的有效性。我们预计多功能 HPOX 纳米粒子具有作为 H2O2 成像剂、治疗剂和与 H2O2 相关疾病的药物输送系统的巨大潜力。
