A Challenge to Cerebral Diseases by Nanomedicine

这项工作的目的是调查我们的纳米颗粒是否被输送到大脑中，以便用于治疗大脑疾病，如阿尔茨海默病、中风、脑出血和脑肿瘤。通过两亲嵌段共聚物的自组装制备了两种类型的纳米颗粒。其中一种在酸性环境下崩解，另一种无论pH值变化都不崩解。稳定的氮氧化物自由基安装在纳米粒子的核心（简称：RNP^N的ph敏感和RNP^O的ph不敏感纳米粒子）。在RNP^O病例中，1-2%的纳米颗粒通过静脉给药进入大脑，而通过口服给药没有进入血流。当聚焦超声与静脉给药同时使用时，积累倾向增加一个数量级。在RNP^N的情况下，静脉给药观察到几乎相同的趋势。有趣的是，5-7%的纳米颗粒在血液中被吸收，其中一部分通过口服RNP^N进入大脑。RNP^N对阿尔茨海默病模型小鼠口服有效。实际上，通过口服RNP^N，病情在4周内几乎完全恢复。

The objective of this work was to investigate if our nanoparticles are delivered to brain in order to use them for cerebral disease such as Alzheimer's disease, stroke, cerebral hemorrhage and brain tumors. Two types of nanoparticles were prepared by self-assembling of amphiphilic block copolymers. One of them disintegrate under acidic environment and the other is no-disintegration regardless of pH change. Stable nitroxide radicals were installed in the core of nanoparticles (abbreviation : RNP^N for pH-sensitive and RNP^O for pH-insensitive nanoparticles). In case of RNP^O, 1-2% of nanoparticle was delivered to brain by intravenous administration, while no uptake into blood stream was observed via oral administration. When focused ultrasound was employed along with intravenous administration, accumulation tendency increased one order of magnitude higher. In case of RNP^N, almost the same tendency was observed vie intravenous administration. It is interesting to note that 5-7% of nanoparticle was absorbed in blood stream and a part of them was delivered in brain via oral administration of RNP^N. Oral administration of RNP^N to Alzheimer's disease model mouse worked effectively. Actually, the condition of a disease recovered almost completely by 4 weeks via oral administration of RNP^N.