Newly synthesized radical-containing nanoparticles (RNP) enhance neuroprotection after cerebral ischemia-reperfusion injury

2，2，6，6-四甲基哌啶-1-氧基(TEMPO)等抗氧化剂对缺血再灌注损伤所产生的自由基具有清除作用。然而，TEMPO的体内半衰期较短，毒性较大。我们开发了一种核壳型纳米粒子，称为含有自由基的纳米粒子(RNP)。我们评估了RNP将Tempo自由基传递到缺血脑和清除脑缺血再灌注损伤中自由基的能力。静脉注射RNPs后6h，可明显减少神经细胞内超氧阴离子的产生。RNPs组大鼠的脑梗塞体积明显小于生理盐水组、胶束组和Tempoll组。RNP治疗可抑制脂质过氧化和蛋白质氧化，并限制Tempo自由基的不良反应，如低血压。RNPs可能是一种很有前途的神经保护剂。

Antioxidant nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) have been investigated for their ability to scavenge free radicals produced by ischemia-reperfusion injury. However, the short in vivo half-life and toxicity of TEMPO was reported. We developed a core-shell-type nanoparticle, termed a radical-containing nanoparticle (RNP). We evaluated the ability of RNP to deliver TEMPO radicals to the ischemic brain and scavenge free radicals in cerebral ischemia-reperfusion injury. RNPs were detected for 6 h after intravenous administration in the ischemic brain, and significantly reduced the production of superoxide anion in neuronal cells. The infarction volumes of rats treated by RNPs were significantly lower than those of rats treated by saline, micelles, and TEMPOL. RNP treatment suppressed lipid peroxidation and protein oxidation, and limited the adverse effects of TEMPO radicals such as hypotension. RNPs could be a promising neuroprotective agent.