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，以便将其用于阿尔茨海默病、中风、脑出血和脑肿瘤等脑部疾病。通过两亲嵌段共聚物的自组装制备了两种纳米粒子。一种是在酸性环境下崩解，另一种是不受pH变化影响而不崩解。稳定的氮氧化物自由基被安装在纳米颗粒的核心(缩写：RNP^N表示pH敏感的纳米颗粒，RNP^O表示pH不敏感的纳米颗粒)。在RNP^O的情况下，1-2%的纳米颗粒通过静脉给药被输送到脑内，而通过口服给药没有被摄取到血流中。当聚焦超声与静脉给药一起使用时，蓄积趋势增加了一个数量级。在RNP^N的情况下，静脉给药也观察到几乎相同的趋势。值得注意的是，5-7%的纳米颗粒被血流吸收，其中一部分通过口服RNP^N进入脑内。口服RNP^N对阿尔茨海默病模型鼠有效。事实上，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.