共轭聚合物延迟荧光增强的新策略及生物成像应用

Designing of polymeric nano-material with delayed fluorescence is one of the important strategies for the growth of diagnosis and treatment of tumor. However, delayed fluorescence materials often suffer from poor water solubility, quenching of delayed fluorescence in water and nonspecific targeting. To improve these defects, a novel smart core-shell conjugated copolymer with thermally activated delayed fluorescence enhancement will be developed in this project for tumor diagnosis and treatment basing on our previous works. Hyperbranched conjugated polymer with controlled branching structure is synthesized through corss-coupling polymerization, and then the core-shell hyperbranched conjugated copolymers are obtained by surface modification with flexible functional hyperbranched polymers. Due to the unique self-assembly of highly branched polymers, the enhancement of delayed fluorescence will be obtained through self-assembly of unimolecular micelle to mutli-aggregates micelles. The relationship between properties of delayed fluorescence and branched struture and self-assmebly behavior of polymer will be investigated systematically. After the grafting of functional groups, such as BSA for quenching of singlet oxygen, biomoleucle for specific targeting, onto the surface of core-shell hyperbranched conjugated copolymer, the specific imaging and diagnosis of tumor cells will be realized. If this project works, it is no doubt that to enrich the delayed fluorescence nano-materials as biomaterials could promote the development of tumor diagnosis and therapy.

构建延迟荧光的聚合物基纳米材料是拓展肿瘤疾病早期诊断与治疗的重要途径之一。现有的延迟荧光材料存在着水溶性差、易淬灭和非特异性识别等问题。本项目拟在原有的工作基础上研制新型的热激活延迟荧光的智能型核壳结构共轭共聚物，并用于肿瘤疾病的诊断与治疗的应用。采用交叉偶联的聚合反应法，制备结构可控的超支化共轭聚合物，并以此为基础合成功能化核壳结构超支化共轭共聚物。借助超支化聚合物特有的高度支化拓扑结构，实现聚合物的单分子胶束的多胶束聚集自组装，获得延迟荧光增强的聚合物纳米胶束。系统阐明超支化共轭聚合物的支化结构和自组装行为对延迟荧光性能的影响。将功能性分子接枝到超支化共轭共聚物表面，利用蛋白中色氨酸对单线态氧的淬灭，生物分子对肿瘤细胞的特异性识别，实现对肿瘤细胞的特异性识别、成像和诊断。通过上述系统研究，有助于丰富延迟荧光材料在生物领域的应用，为肿瘤的诊断和治疗提供新的途径。

星状共轭共聚物的构建是发光性能增加的共轭聚合物材料在生物医药领域应用的重要途径之一。本项目拟在已有的星状共轭聚合物的基础上，利用共轭聚合物单体在给电子单元和吸电子单元的调整与选择，实现新型超支化共轭聚合物的特殊发光性质，以此构建具有刺激响应性的星状共轭共聚物体系，发展一类新型智能药物输送体系，以期在肿瘤特异性识别和治疗方面获得应用。首先，系统研究了一系列的星状共轭共聚物的合成，纯化，其次，考察其在细胞内的特异响应性及其响应机理，最后，探索该聚合物用作智能药物输送体系在生物医药领域应用的可行性。实验结果表明，1）调节单体的配比得到端基可控的超支化共轭聚合物，以便亲水性聚合物的接枝形成星状共轭共聚物；2）利用改变单体的供体和受体基团，得到不同光学性质的超支化共轭聚合物，包括延迟荧光，双光子荧光和荧光能量共振转移；3）星状共轭共聚物中的超支化共轭聚合物核，亲水性聚合物壳，及其两者偶联接枝基团均可实现刺激响应性，均可实现对氧，温度和和过氧化氢具有特异响应性质；4）一系列星状共轭共聚物在水中具有优异的光学性质，从而实现对体外和体内的肿瘤特异性识别、诊断和光动力治疗的应用。这类星状共轭共聚物结构具有普适性，借助分子设计改变聚合物结构、光学性质、功能性等，在生物医用领域极具应用前景。