刺激响应聚氨基酸高分子的合成与应用

Biodegradable stimuli-responsive polypeptide materials are important and promising biomaterials with extensive applications. In this proposal, we aim to prepare several stimuli-responsive polypeptides starting from amino acids. Firstly, new functional amino acids monomers containing different responsive units will be designed and synthesized using natural amino acids as starting materials. Then, various stimuli-responsive polypeptides will be prepared from these new monomers via controlled ring opening polymerization (ROP) of amino acid N-carboxyanhydride (NCA) monomers. For these new polypeptide materials, the correlation between thermo-response properties and composition, monomer structure, secondary structure of polypeptides block will be systematically investigated. Secondly, peptide amphiphiles (PA) and thermo-responsive copolypeptides will be prepared via ROP of NCA using alkyl amine and PEG-NH2 as macroinitiator, respectively. The peptide amphiphiles are designed to form injectable hydrogel while the thermo-responsive amphiphiles are able to form thermo-gel. This method will significantly improve the efficiency of synthesis and decrease the cost of peptide synthesis from Solid Phase Peptide Synthesis. Moreover, different NCA monomers can be combined to make multiple stimuli-responsive hydrogels such as thermo- and redox- dual response hydrogels. Thirdly, we will develop new fabrication process to make well-defined nanogel particles based on synthetic copolypeptides containing multi functional groups. Optimized conditions will be established to realize control over nanogel particle sizes, size distributions and functionalities. For all these materials, the effects of polypeptides composition, chain length, secondary structure and functional groups on hydrogel properties will be systematically investigated. The mechanism of turning secondary structures of responsive polypeptide segment will be addressed. The obtained information will guide us the polymer design and synthesis and also help us to optimize materials properties. Finally, biomedical applications of these kinds of injectable hydrogels in cell therapy and controlled drug release will be investigated.

生物降解的刺激响应聚氨基酸是一类具有重要应用前景的生物医用高分子，本项目以氨基酸为核心研究对象，设计合成多种功能化氨基酸单体，通过可控开环聚合来制备刺激响应性聚氨基酸。系统研究新型刺激响应聚氨基酸的环境刺激机制及调控，理解在相转变过程中氨基酸侧链的化学结构和聚氨基酸二级结构对刺激响应性的影响。进一步探索如何实现聚氨基酸构象的可控转变以及聚氨基酸分子间氢键相互作用的调控。通过可控开环聚合批量合成聚氨基酸两亲凝胶分子，用于构筑可注射水凝胶，解决凝胶固相合成成本高的问题；通过开环聚合合成温度响应两亲分子，用于构筑温敏水凝胶；在温度响应两亲分子基础上，设计增加其他刺激响应的聚氨基酸模块，用于构筑多重响应水凝胶。探索可注射水凝胶在皮下注射药物缓释、细胞培养和细胞疗法中的应用。利用合成聚氨基酸来可控制备纳米水凝胶颗粒用于药物释放载体。

刺激响应性生物可降解聚氨基酸是一类重要的生物医用高分子材料。按照项目研究计划，我们以聚氨基酸为核心研究对象，设计合成了多种刺激响应性（光、pH、离子、氧化还原）氨基酸单体，通过可控开环聚合以及后修饰法来制备刺激响应性聚氨基酸。进一步系统研究了刺激响应聚氨基酸的环境刺激机制及调控，理解在相转变过程中氨基酸侧链的化学结构和聚氨基酸二级结构对刺激响应性的影响，并探索如何实现聚氨基酸构象的可控转变以及聚氨基酸分子间氢键相互作用的调控。此外，我们还结合了多种刺激响应的聚氨基酸模块，用于构筑多重响应水凝胶，通过可控开环聚合批量合成聚氨基酸两亲凝胶分子，用于构筑可注射水凝胶，我们构筑了刺激响应性纳米凝胶，并探索其生物应用。利用合成刺激响应性聚氨基酸来可控制备纳米水凝胶颗粒用于药物、蛋白质释放载体。