含生物可降解嵌段的氢键键合两亲性超分子共聚物的胶束化与溶液自组装

Nucleobase is an ideal building block for supramolecular polymers and constructing the nucleobase H-bond is an efficient approach for the controllable and programmable molecular self-assembling, because of the high selectivity and reversibility of H-bond between the nucleobase pairs. In this project, we would like to select poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) as the model blocks and synthesize the nucleobase-terminated PLA and PEG. The nucleobase H-bond connected copolymeric micelles will be prepared through the solution self-assembly of the PLA:PEG supramolecular amphiphilic block copolymer in aqueous media. The structure, morphology, and physical properties (e.g., micellar stability and stimuli responsivity) will be investigated via DLS, SLS, TEM, AFM, and synchrotron radiation SAXS techniques. The effects of crystallization, stereocomplex crystallization of the core-forming block, connection mode between the hydrophilic and hydrophobic blocks, and the environmental conditions (e.g., temperature and pH) on the structure/morphology and physical properties of the H-bond connected micelles will be investigated. The stimuli-responsive supramolecular copolymer micelles prepared in this work will find potential applications in the controlled drug release and chemical sensing. This study will provide a new approach to analyze the precise structure of non-covalently connected copolymer micelles via the synchrotron radiation SAXS, as well as tune their structure/morphology, physical property, and function by changing the crystalline structure of the core-forming blocks. The mechanistic investigations conducted in this study will help to further understand the principle and theory of the self-assembly behavior of soft matter with the hierarchical and weak non-covalent interactions.

由于核酸碱基互补氢键高度的选择性和可逆性，核酸碱基是构筑超分子聚合物的一种理想结构单元，也是实现可控自组装的有效途径。本课题将以聚乳酸（PLA）和聚乙二醇（PEG）为例，制备核酸碱基为端基的PLA和PEG，利用PLA:PEG两亲性超分子共聚物的溶液自组装，制备氢键键合聚合物胶束材料。将利用DLS、SLS、TEM、AFM和同步辐射SAXS研究胶束的结构形貌和物理性能（如稳定性、环境响应性），将研讨共聚物中成核嵌段（复合）结晶化、亲/疏水嵌段间键合方式、外界条件（如温度、pH值）对氢键键合胶束结构形貌和性能的影响规律及机理。本项目制备的环境响应性超分子聚合物胶束将有望用于药物可控释放、化学传感器领域。本研究将提供一种同步辐射SAXS法分析非共价键合胶束精密结构和通过控制成核嵌段聚集态结构调控胶束结构和物理性能的新方法，将有助于进一步理解具有多层次相互作用、弱键键合软物质体系自组装的规律与理论。

由于其高度选择性和可逆性，多重氢键是构筑超分子聚合物的一种理想结构单元，也是实现可控自组装的有效途径。与通常的嵌段共聚物类似，氢键键合的两亲性嵌段共聚物在水溶液中可自组装形成胶束。对于超分子胶束体系，胶束的结构和性质将受亲/疏水链段间键合形式、成核链段结晶影响，但这些影响规律与机理目前尚不清楚。本项目以生物可降解聚酯[如聚乳酸（PLA）、聚乙丙交酯（PLGA）]和聚乙二醇（PEG）为模型的亲、疏水嵌段，制备了胸腺嘧啶（THY）/二氨基三嗪（DAT）三重氢键、2-脲基-4[1H]嘧啶酮（UPy）四重氢键超分子单元端官能化的PLA、PEG和PLGA-PEG-PLGA，利用两亲性超分子共聚物的溶液自组装，制备了多重氢键键合的共聚物胶束。利用同步辐射SAXS等技术表征了共价键键合和超分子共聚物胶束的结构，建立了核壳胶束的散射模型，基于溶液SAXS分析得到了胶束的精密结构信息，建立了氢键键合超分子共聚物胶束结构与性能（如环境敏感性、药物释放行为等）之间的关系。. 发现氢键键合超分子胶束的结构和性能受成核链段结晶、立构复合结晶、亲/疏水嵌段间键合方式显著影响。成核链段PLA的结晶可提高胶束的稳定性，降低胶束的降解速率和药物释放速率，成核链段PLA的立构复合结晶可提高胶束的缔合度和核层分子链的堆积密度。与通常的共价键键合共聚物胶束相比，超分子共聚物胶束的缔合度和粒径较大，这使其具有较大的载药量。另外，多重氢键基团的引入影响共聚物胶束的环境敏感性，PLGA-PEG-PLGA链端引入UPy基团形成超分子共聚物后，其胶束的最低临界溶解温度降低。本项目所制备的环境响应性超分子共聚物胶束有望用于药物可控释放等领域。基于同步辐射溶液SAXS等技术，本研究建立了分析共价键和非共价键合共聚物胶束精密结构，以及通过控制成核链段结晶凝聚态结构调控胶束结构和物理性能的方法，揭示了两亲性共聚物中亲/疏水链段间键合形式、成核链段结晶对其胶束化和胶束结构的影响规律与机理，将有助于进一步理解具有多层次相互作用、弱键键合高分子体系自组装的规律与理论。