胚胎干细胞在帕金森病的细胞替代治疗中具有很好的应用前景。如何提高胚胎干细胞向多巴胺神经元的分化效率具有重要的科学意义和应用价值。我中心的前期研究显示，miR-132反向调控胚胎干细胞向多巴胺神经元的分化。因此，利用miR-132反义核酸沉默内源性miR-132将达到促进分化的作用。但常规方法转染效率不高且有一定毒性。我的前期工作已证明，纳米金能够低剂量、高效率的递送功能性核酸进入细胞且显著提高其生物活性(Angew.Chem.Int.Ed., IF=13.734)。据此，本项目拟采用天然多聚腺嘌呤嵌段核酸与纳米金自组装的方法，合成不同表面核酸密度的miR-132反义核酸-纳米金复合物，评估其促进胚胎干细胞向多巴胺神经元分化能力，阐明该复合体系的生物学效应和对靶基因的作用机制并深入论证其应用价值。该研究结果将为利用功能性纳米复合体系高效提高多巴胺神经元分化效率提供理论依据和实验支持。

Embryonic stem cells have good application prospect in cell replacement therapy in Parkinson's disease. However, how to improve the efficiency of dopamine neurons differentiation from embryonic stem cells has important scientific significance and application value. Previous study of our research center showed that miR-132 negatively regulated the differentiation of embryonic stem cells into dopamine neurons. Therefore, using miR-132 antisense nucleic acid silencing of endogenous miR-132 could promote the differentiation. Conventional transfection methods are not efficient enough and have certain toxicity. My pre-work confirmed that gold nanoparticles could highly efficient delivery of nucleic acids into cells at low dose, and significantly increase the biological activity of nucleic acid(Angew. Chem. Int. Ed., IF=13.734). In this project, we intend to develop gold nanoparticle- based polyvalent miR-132 antisense nucleic acid nanoconjugates by using self-assembled method, and study its ability to promote embryonic stem cells differentiation into dopamine neurons. After treatment with miR-132 antisense nucleic acid-gold nanoparticle complexes, we will elucidate the biological effect of embryonic stem cells differentiate into dopamine neurons and the underlying mechanism to target gene, and in-depth evaluate its application value. The results of the study will provide theoretical basis and experimental support for using functional nano-complexes to efficiently improve the dopamine neuronal differentiation efficiency.