具有聚集诱导发光性能的pH响应聚合物的合成与性能研究

Fluorescent polymeric nanopaticles with pH-responsive property are promising for tumor cell imaging, detecting, and curing. However, heretofore, satisfactory results are rarely achieved due to the limitation of aggregation-caused queching (ACQ) effect of organic luminophores. Recently, aggregation-induced emission (AIE) has emergied to be an effective method to tackle the ACQ problem. The main purpose of this project is to prepare a series of polymers with both AIE and pH-responsive properties for the detection of tumor cells, by using reversible addition-fragmentation chain transfer (RAFT) polymerization. The AIE character of the polymers can offer high fluorescent intensity for their corresponding nanoparticles, the pH-responsive feature of them can tell the normal and tumor cells apart straightforwardly by exhibiting dual-color emission due to their different pH values. In this project, the influenece of molar ratio of hydrophilic and hydrophobic chain segments will be investigated and the mechanism for the pH-responsive property of the polymers will be studied. It is expected to provide a new strategy for designing efficient fluorescent probe materials for tumor cell detection through the systematic study of the relationship of molecular structure, nanoparticle morphology, pH-repsonsive property and fluorescent character of the polymers, as well as the interaction of nanoparticles and tumor cells. Therefore, this project has important theoretical and actual value.

pH响应性荧光聚合物纳米微粒在肿瘤细胞成像、检测和治疗等方面极具应用潜力，但当前对构筑纳米微粒时所产生的聚集荧光猝灭（ACQ）问题仍缺乏有效的解决方法，而聚集诱导发光（AIE）聚合物能解决ACQ问题。为此，本项目拟通过RAFT聚合合成一系列具有AIE性能、在肿瘤细胞和正常细胞pH（5.0-7.4）区间具有双荧光发射的聚合物，并将其应用于肿瘤细胞的荧光探针超敏检测。在研究AIE疏水段结构和亲疏水段比例对聚合物pH响应的影响基础上，探讨聚合物pH响应机制；调控聚合物的化学结构，系统研究不同pH条件下的AIE聚合物纳米微粒的形貌和荧光发射性能，从而建立聚合物结构、pH响应、纳米微粒形态和荧光特性四者之间的关联,同时探讨聚合物纳米微粒与肿瘤细胞之间相互作用以及荧光探针响应过程，建立快速检测肿瘤细胞的实验方法。本项目为科学地设计肿瘤细胞荧光探针材料提供了一个新思路，具有重要的理论与应用价值。

荧光聚合物纳米微粒在肿瘤细胞成像、检测和治疗等方面极具应用潜力，但当前对构筑纳米微粒时所产生的聚集荧光猝灭（ACQ）问题仍缺乏有效的解决方法，而聚集诱导发光（AIE）聚合物能解决ACQ问题。本项目通过RAFT技术将水溶性乙烯单体和一种新的AIE乙烯单体聚合得到了系列嵌段共聚物，该系列两亲性嵌段共聚物在水中可以自组装成具有良好分散性的荧光聚合物纳米粒子。所制备的纳米粒子在水溶液中能够发射出强烈的绿色荧光，并具有较高的荧光量子产率和较低的临界胶束浓度，由于其具备良好的细胞相容性和光稳定性，用于细胞成像时具有明显优势。此外，在合成AIE单体的过程中，合成了一种含有四苯乙烯基团和苯并噻唑基团的化合物，该化合物具有优异的AIE性能和高的固态荧光量子效率，并呈现出明显的压致变色和酸致变色特性，机理研究表明，其酸致变色主要是由苯并噻唑的质子化使分子的ICT效应增强引起的。本项目还高产率地合成出了系列具有不同烷基链长度和卤素末端的烷基吩噻嗪氟苯乙腈衍生物中，该系列化合物具有明显的聚集诱导发光性能和依赖于烷基链与卤素基团的压致变色性能，只有具有合适的结晶性、恰当的分子极性和能隙差，化合物才能具有明显的压致变色性能。本项目研究拓宽了AIE材料的种类和应用范围，为科学地设计细胞成像荧光探针分子提供了新思路，具有重要的理论与应用价值。