Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice

Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8) mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.过量生成的活性氧（reactive oxygen species）与年龄相关性神经退行性疾病密切相关。本研究探究了通过口服给药的氧化还原纳米颗粒（redox nanoparticles）清除大脑内活性氧的效果——该纳米颗粒由带有抗氧化性氮氧自由基（nitroxide radicals）的氧化还原聚合物自组装制备而成——能否促进17周龄快速老化易感小鼠（senescence-accelerated prone mouse, SAMP8）的认知功能恢复。口服该氧化还原纳米颗粒后，其可在胃部发生解离，释放出的氧化还原聚合物经小肠吸收入血，最终抵达大脑。经过为期1个月的给药治疗后，与低分子量氮氧自由基治疗组相比，氧化还原纳米颗粒治疗组的SAMP8小鼠大脑内氧化应激水平显著降低，认知损伤得到改善，存活神经元数量也有所增加。此外，氧化还原纳米颗粒治疗未表现出任何可检测到的毒性。上述研究结果表明，氧化还原聚合物纳米治疗制剂在神经退行性疾病的治疗中具有潜在应用潜力。