自组装高分子囊泡微纳米马达精准诱导神经干细胞生长分化

Structure simplicity and limited functionality are the bottlenecks for the development of micro/nanomotor field. To solve the problem, a self-assembly approach is proposed to integrate multiple function units (biodegrading, autonomously moving, neural stem cell stimulating), obtaining a multifunctional polymersome motor system. The motor is composed of a biodegradable polymersome, with magnetic nanoparticle encapsulated in the cavity and neurotrophic factor/glucose oxidase functionalized on the surface. Glucose oxidase can catalyze the decomposition of glucose in solution, thus providing driving force for the motor system. With an external magnetic field, the magnetic nanoparticle encapsulated motor can achieve guided motion and reach specific point of neural stem cell. The stimulation position of the neurotrophic factor on the motor, as well as the morphology, correlates with the growth/differentiation direction of the neural stem cell. By varying the stimulation position of motor, the growth/differentiation of the neural stem cell can be precisely controlled. With the capability of controlled moving and cell growth/differentiation guiding, the motor system can provide input signal precisely at single neural stem cell level. It not only provides a solution to the problem that neural stem cell growth/differentiation lacks precise control but also facilitates the application of micro/nanomotor in the biomedical field.

目前人工微纳米马达结构相对简单、功能比较有限是领域发展面临的重要问题。针对这一问题，本项目拟通过自组装，集成多种结构及功能组分，制备出集生物可降解、运动可控、神经干细胞刺激多功能为一体的复合高分子囊泡微纳米马达。马达主体为不同形貌的可降解高分子囊泡，内部包载磁性纳米粒，表面修饰葡萄糖氧化酶和神经营养因子。葡萄糖氧化酶以溶液中的葡萄糖为底物，通过催化反应驱动整个系统。由于包载了磁性纳米粒，马达在磁场控制下运动方向可控，能准确到达神经干细胞任一指定位点，通过表面的神经营养因子激活细胞表面受体，联合自身形貌，实现高时空分辨的神经干细胞定点刺激。调节刺激位点会影响细胞生长与分化方向，因而能通过马达精准诱导细胞的生长分化。本体系整合可控运动、神经干细胞诱导等多种功能，在单细胞水平上实现信号准确输入，有望解决当前神经干细胞生长分化诱导缺乏精准控制的问题，对推动微纳米马达在精准医疗上的应用也有重要意义。

人工微纳米马达结构简单、功能有限是领域的重要问题。针对这一问题，本项目通过生物杂交技术和自组装，集成多种结构及功能组分，制备出集生物可降解、运动可控、神经干细胞刺激多功能为一体的复合微纳米马达。通过在螺旋状藻马达系统中引入磁响应性四氧化三铁材料，实现了马达在外加磁场下的精准运动，从而定点到达预定的类神经干细胞表面。将超声与马达表面压电钛酸钡相结合，利用超声所产生的机械应力来诱导马达表面的压电材料，使其产生直流电输出，从而促进细胞在刺激位点形成轴突并实现分化。这是目前率先利用磁控压电功能来精准诱导类神经干细胞精准分化的报道。该体系巧妙地整合了可控运动、无创诱导神经干细胞分化等多种功能，在单细胞水平上实现了信号的精准输入，有望解决当前神经干细胞分化缺乏精准控制的挑战。