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

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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.