Development of radical-containing Nan particle for therapy and imaging of oxidative stress injuries

我们开发了由自组装两亲嵌段共聚物（PEG-b-PMNT；聚（乙二醇）-b-聚[4-（2,2,6,6-四甲基哌啶-1-氧基）胺甲基苯乙烯]）制备的ph敏感的含氮自由基纳米颗粒（RNP^N）。由于PEG-b-PMNT疏水段的氨基质子化，这种自组装的RNP^N在pH低于7.0时分解，从而提高了ROS清除活性。采用小鼠肾缺血再灌注急性肾损伤模型，评价RNP^N的保护作用。电子自旋共振谱证实了血流中聚合物胶束的形成和损伤肾区RNP^N的分解。由于这些特性，与低分子量的一氧化二氮自由基衍生物相比，RNP^N具有极高的ROS清除活性和肾脏保护作用。有趣的是，由于非靶向区域RNP^N核心的氮氧化物自由基被区隔化，氮氧化物自由基的副作用被明显抑制。在此基础上，该系统有望成为治疗各种氧化应激损伤的新药物。

We have developed pH-sensitive nitroxide radical-containing nanoparticles (RNP^N) prepared by a self-assembling amphiphilic block copolymers (PEG-b-PMNT ; poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]). This self-assembled RNP^N disintegrates at pH below 7.0 because of a protonation of amino groups in the hydrophobic segment of the PEG-b-PMNT, thereby resulting in an improvement in ROS scavenging activity. Using a renal ischemia-reperfusion induced acute kidney injury model in mice, the protective effect of RNP^N was evaluated. The formation of polymeric micelle in bloodstream and disintegration of RNP^N in injured kidney area were confirmed by electron spin resonance spectra. Due to these characters, the RNP^N showed extremely high ROS scavenging activity and renal protective effect, compared to low molecular weight nitoroxide radical derivatives. It is interesting to note that the side effect of nitroxide radicals was markedly suppressed due to the compartmentalization of nitroxide radicals in the core of RNP^N in untargeted area. On the basis of these results, this system is expected as a new medication for therapy of various oxidative stress injuries.