开环聚合构筑酶响应性聚氨基酸基荧光探针

Improving and expanding the in vivo function of small-molecule fluorescent probes by integrating with the stimuli-responsive polymer, which could help us understand the relationship between structure and function of polymer, and promote the development of the responsive polymer in the field of medical detection and diagnosis. In this proposal, we aim to integrate the enzyme-responsive polypeptides with the enzyme-responsive small-molecule fluorescent probe. The enzyme-responsive polypeptides will be prepared via controlled ring opening polymerization (ROP) of amino acid N-carboxyanhydride (NCA) monomer and post-polymerization modification of side chains. The effects of enzyme-responsive polypeptides chain length, secondary structure, hydrophobicity-hydrophilicity ratio, and polymeric assembly will be investigated systematically on the enzyme-responsibility of small-molecule fluorescent probes. The coordination mechanism of polypeptides-based fluorescent probes response to enzyme will be addressed to increase the sensitivity and selectivity. The obtained information will guide us the new polypeptides design and synthesis to optimize the enzyme-response properties of polypeptide-based fluorescent probes. Finally, the enzyme-responsive polypeptides- based fluorescent probe will be further investigated as diagnosis & therapy systems for tumor.

从响应性高分子材料设计的角度，完善和拓展荧光探针的功能，不仅能够更好的理解高分子本身的结构与功能的关系，还能推动刺激响应性高分子在医学检测平台技术的发展。整合小分子荧光探针原位诊断的优势，以及酶刺激响应聚氨基酸材料的结构响应特性，本项目拟采用活性N-羧酸酐（NCA）可控开环聚合并结合后修饰等手段，制备酶刺激响应性聚肽基荧光探针。我们将通过分子设计和组装，调控聚肽高分子的酶刺激响应性与荧光探针功能的集成与协同，不断优化结构，探索酶响应性聚肽基荧光探针在肿瘤诊断的应用。

本项目以酶响应聚氨基酸作为研究对象，去完善和拓展荧光探针的功能，推动诊疗平台技术的发展。本项目在从材料设计上进行创新，采用活性N-羧酸酐（NCA）可控开环聚合并结合后修饰等手段，制备了酶响应聚氨基酸。考察了分子量和分子量分布对二级结构、组装结构的影响，并实现对肿瘤微环境异常表达酶的快速响应。同时，将近红外荧光探针功能性整合到酶响应聚氨基酸，考察了功能的集成与协同，在小鼠模型上实现了对肿瘤选择性的诊疗。更有趣的是，在本项目实施过程中，我们发现荧光探针的分子结构、超分子组装结构和诊疗性能的构效关系，为下一代探针设计提供了实验基础和理论依据，可以拓展刺激响应性材料在医学领域的应用。