新型两亲性氟硼二吡咯类染料的设计合成及其自组装纳米生物探针构建

基于有机染料的纳米生物探针由于其重要应用价值已成为当前的研究热点。本项目通过新型染料的分子设计与合成、染料分子自组装特性研究、纳米探针制备及生物成像应用这三个层面的研究，对自组装纳米生物探针的构建及性能优化的新思路进行探索。为此，研究中将合成一系列具有不同共轭体系结构、疏水片段、亲水片段的氟硼二吡咯类近红外染料，通过调节分子化学结构对染料的光学性质及亲疏水特性进行调控，进而在染料分子亲水片段部分引入具有酶响应、pH响应或肿瘤靶向等功能的多肽单元；在此基础上研究新型两亲性染料分子自组装过程的热、动力学特性，考察染料纳米聚集体的光学性质及纳米形貌，阐明影响染料分子自组装行为的主要因素；进一步开展纳米生物探针制备研究，并以探针进行细胞及活体荧光或荧光-光声双模成像研究，利用具有多肽功能单元的染料分子实现纳米探针对特定生物条件的响应性，从而优化探针性能并为其应用奠定基础。

In recent years, the organic dye-based nano-bioprobes have received tremendous attention owing to their promising application potentials. This research project aims to explore the construction and the performance optimization of self-assembled nano-bioprobes according to three aspects of research, including the design and synthesis of new functional dyes, the self-assembly properties of the new dyes, and the preparation as well as bioimaging studies of the nanoprobes. In this project, a serial of new NIR BODIPY dyes with various conjugation structures, hydrophobic segments，and hydrophilic segments will be synthesized. The optical properties and the hydrophobic/hydrophilic characters of the dyes will be modulated by chemical structure modification of the molecules. Furthermore, peptide units with enzyme responsive, pH responsive, or tumor targeting functionalities will be introduced as hydrophilic segments into the dye molecules. Based on these studies, the thermodynamic and kinetic properties of the self-assembly process of the dyes will be investigated. The optical properties and the morphology of the dye nanoaggregates will be studied. The main factors which influence the self-assembly behavior of the dyes will be elucidated. In further research, the nanoprobes will be prepared and applied for fluorescence or fluorescence–photoacoustic bimodal imaging studies in vitro or in vivo. Especially, the peptide functionalized dye molecules will be used to obtain responsive nanoprobes for specific biological events. Accordingly, the performance of the nanoprobes will be optimized and further applications of these nanoprobes will become prospective based on the research in this project.