Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury

[摘要] The main culprit in the pathogenesis of ischemia/reperfusion (VR) 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 copolyoxalaie nanoparticles using a murinc model of hind limb l a injury. The nanoparticles arc composed of hydroxybenzyl alcohol (HBA)-incorporating copolyoxalatc (HPDX) that, in the presence of H2O2, degrades completely into three known and safe compounds, cyclohexanedimethanol, HBA and CO2. HPDX 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. HPDX 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, HPDX 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 HPDX nanoparticles have great potential as H2O2 imaging agents, therapeutics and drug delivery systems for H2O2 associated diseases. (C) 2013 Elsevier B.V. All rights reserved

[发布日期] 2013-12-28

[关键词] Theranostics;Bioimaging;Drug delivery;Polymer;Hydrogen peroxide