有序规整聚肽组装体的可控制备及机制探究

Polypeptide self-assembled aggregates have a wide range of potential applications in the fields of biomedicine and nanoscience. However, their applications are limited due to their irregular morphologies and uncontrollable sizes. This project will start from the polymer molecular design and synthesis, and block copolypeptides with different topologies are prepared through the optimization of polymerization conditions. Then, using the solution self-assembly method, the self-assembled aggregates with regular morphologies and controllable sizes based on the block copolypeptides are prepared through precisely controlling the experimental conditions, and rationally "tailored" from the one-dimensional fiber-like cylindrical micelles to two-dimensional plate-shaped structures. Furthermore, the applications of the assembled aggregates are explored in some fields such as biological drug loading and detection, and the effects of the shape and size of the assembled aggregates on the therapeutic effect are evaluated. Their practical applications will be expanded in many fields such as biomedicine, nanoscience and materials science, etc. On the other hand, by exploring the self-assembly process, the controllable mechanisms on the morphology, size and dimension of the self-assembled aggregates are revealed. The implementation of this project can further lay the foundation for the preparation, manipulation and application of the multidimensional material preparation.

聚肽组装体在生物医学和纳米科学等领域存在广泛的应用，但其组装体形貌不规整，尺寸难于控制限制了它的应用范围。本项目从聚合物分子设计、合成出发，优化聚合反应条件，制备出不同拓扑结构的聚肽嵌段共聚物。利用溶液自组装法，精确控制实验条件，调控聚肽嵌段共聚物组装体的形貌和尺寸，制备出形貌规整均匀、尺寸可控并均一的聚集体，从一维的纤维棒状胶束到二维的片状结构进行“量身定制”。进而开展其组装体在生物载药、检测等方面的应用，评估组装体的形貌和尺寸对疗效的影响规律，拓展其在生物医学、纳米科学和材料科学等领域的实际应用。并通过探索其自组装行为，揭示调控其组装体形貌、尺寸和维度的机制，进一步为多维材料的制备、调控和应用奠定一定的基础。

本项目采用NCA(α-氨基酸-N-羧基内酸酐)开环聚合法，制备出不同端基、不同分子量的聚(L-谷氨酸苄酯)（PBLG），较为系统地开展了均聚肽PBLG在选择性溶剂中的自组装行为，明确了其自组装机制，研究结果表明：聚肽PBLG的聚二级结构α-螺旋及肽键的亲水性对自组装体的形成和稳定起到关键性的作用。并通过改变浓度、链长等可获得不同结构的自组装体：纺锤形胶束、棒状胶束、纳米带、螺旋线和圆环状胶束等超分子结构。合成出均聚肽聚（Nε-苄氧羰基-L-赖氨酸）（PZlys）和三种不同组份比例的共聚肽P(BLG-co-Zlys)，系统地开展了它们在选择性溶剂水中的自组装行为，明确了侧链亲水基团是均聚肽PZlys组装形成囊泡的关键因素。合成不同聚合度的均聚肽聚(β-苯乙基-L-天冬氨酸酯)（PPLA），考察了它们的自组装行为，并组装形成具有类似病毒衣壳结构的囊泡结构，详细地研究研究了其形成机制，研究结果表明：聚合度是决定形成具有类似病毒衣壳结构的囊泡结构的关键因素。. 另一方面，联合氨基酸NCA 开环聚合法、原子转移自由基聚合法(ATRP)和点击化学(click chemistry)等方法，合成了一系列结构确定嵌段共聚肽，较为系统地开展了共聚肽在选择性溶剂中的自组装行为，通过改变浓度、链长等可获得不同结构的自组装体：球型胶束、囊泡、大囊泡、梭形胶束、棒状胶束和3D长方体胶束和螺旋胶束等超分子结构，并可控制备出长度大小不同的纺锤体胶束和具有三维结构的长方体胶束等。. 通过本项目的研究，可为均聚物的自组装行为，特别是含极性基团、具有二级构象（如α-螺旋）的均聚物自组装和含该类聚合物的嵌段共聚物自组装提供了参考。特别是可以通过聚合物浓度来调控胶束的长度为组装体的可控制备供实验和理论依据，拓展大分子自组装领域，对该类材料的基础研究和实际应用奠定基础。