帕金森病（PD）是第二种常见的神经退行性疾病，目前无论是药物治疗还是外科手术，都不能从根本上治愈疾病。由于黑质致密部多巴胺能（DA）神经元的损失是PD的病理学标志，NSCs移植治疗为治愈PD带来新曙光。本项目拟制备水溶性、正电荷、强荧光的g-C3N4纳米片，在前期工作基础上，充分利用g-C3N4纳米片特异的光电性能及高比表面积，构建双基因siSOX9/pNurr1协同输送系统，实现siRNA和质粒DNA同时转染，级联式诱导小鼠胚胎NSCs定向分化成DA能神经元，并进一步通过脑内立体定位移植治疗MPTP损伤的小鼠PD模型。项目拟从以下三方面进行深入系统地探究：g-C3N4在光照条件下对小鼠胚胎NSCs的增殖、分化的作用及机制；pNurr1-siSOX9-g-C3N4在光照条件下诱导小鼠胚胎NSCs定向分化成DA神经元的性能及机制；g-C3N4构建的双基因协同输送系统应用于小鼠PD模型治疗潜能

Parkinson's disease (PD) is the second most common neurodegenerative disease. For the moment, neither drug therapy nor surgery can cure this disease fundamentally. Neural stem cells(NSCs) transplantation become a new view for PD, because lossing of the dopaminergic neurons(DA) in substantia nigra pars compacta, which is a pathological marker of PD. In this study, a g-C3N4 nanosheets with water solubility, positive charge and strong fluorescence is prepared in our previous work. and then the specific photoelectric properties and high specific surface area of g-C3N4 nanoplatelets are fully utilized to construct a dual-gene siSOX9/pNurr1 co-delivery system to achieve dual transfection of siRNA and plasmid DNA simultaneously. g-C3N4 nanosheets are used to co-deliver siSOX9 and pNurr1 into the embryoinc mouse NSCs, which enhance the directional differentiation dopaminergic neuron of NSCs, and further treatment of MPTP-injured mouse model of PD by stereotactic transplantation in the brain. The project will be plan to conduct in-depth systematic exploration from the following three aspects: the effect and mechanism of g-C3N4 nanosheets on the survival, proliferation and differentiation of mouse embryonic NSCs under light stimulation; the performance and mechanism of pNurr1-siSOX9-g-C3N4 system that induce directional differentiation into DA neurons of mouse embryonic NSCs under light stimulation; the therapeutic potential of brain transplantation in mouse model with the dual gene co-delivery system constructed by g-C3N4 nanosheets.