基于识别烟碱型乙酰胆碱受体α7的分子印迹聚合物脑靶向载体初步研究

Construction of the brain-targeting drug carrier through imprinting of nicotinic acetylcholine receptor α7

本文通过构象表位策略制备一种新型脑靶向载体系统并对其进行初步评价。以丙烯酰胺和N,N'-亚甲基双丙烯酰胺为载体材料,烟碱型乙酰胆碱受体α7的N端表位多肽为模板分子,经聚合反应及模板洗脱制备分子印迹纳米粒。通过粒度仪和透射电镜对制得的聚合物纳米粒进行表征,并通过靶细胞摄取和体内荧光活体成像实验考察其靶向性。结果表明,所得聚合物纳米粒粒径较小(42.1±4.3 nm),分布均一,能有效识别表位多肽且具有良好的体内外靶向性。本研究基于分子印迹原理设计并制备具有脑靶向性的印迹聚合物纳米载体,有望为药物脑部递送及相关疾病治疗提供新思路。

In this study, a novel brain-targeting carrier was made via conformational epitope imprinting. Acrylamide and N,N ＇-methylene bisacrylamide was used as carrier materials and the N-terminal epitope of nicotinic acetylcholine receptor α7（n Ach R α7） was tested as a template molecule, and the polymer nanoparticles were obtained after polymerization and template removal. The nanoparticles were investigated by particle size analyzer and transmission electron microscopy（TEM）. Their targeting capabilities were investigated with a cell uptake assay in vitro and fluorescence imaging in vivo. The results suggest that the nanoparticles had a small particle size（42.1 ± 4.3 nm） with a homogeneous distribution, and good targeting properties in vitro and in vivo. We have made the molecularly imprinted polymer nanoparticles with brain targeting capability, which represents a new tool in the treatment of brain diseases.