阿尔茨海默症(AD)作为一种常见的老年疾病，迄今仍无药物能完全治愈。研究表明：溶酶体粘度和Aβ聚集体与AD发病机理密切相关；若能对二者同时检测，则为AD发病机理研究提供有效工具。但是，目前能同时响应溶酶体粘度和Aβ聚集体的双功能荧光探针仍鲜有报道。与此相关，申请人前期研究表明：meso位含可旋转C=C双键的氟硼二吡咯(BODIPY)类染料具有较好的粘度和Aβ响应性能。基于此，本课题拟设计合成BODIPY近红外双功能荧光探针，使探针集meso位C=C双键可旋转(微环境响应)和D-π-A(易于结合Aβ聚集体)两种结构特征于一体，在溶酶体粘度增大和Aβ聚集体存在时，分子柔性降低，自由旋转受阻，通过不同程度的“荧光增强”和“波长红移”，实现溶液检测和生物成像。通过筛选和优化分子结构，阐明构效关系，以期开发新颖的溶酶体粘度和Aβ聚集体近红外双功能荧光探针，为AD发病机理研究提供新思路和方法。

Alzheimer's disease (AD), as a common elderly disease, has not been completely cured by drugs. Currently, it has been found that lysosomal viscosity and Aβ aggregates are two factors closely related to AD, and if they can be simultaneously detected, this field of research will provide an effective tool for AD’s pathogenesis research. However, the dual-functional fluorescent probes for simultaneous detection of lysosomal viscosity and Aβ aggregates are still rare. In applicant's previous research, a rotatable BODIPY dye with C=C double bond at the meso site has been designed and synthesized, which showed good response towards viscosity and Aβ aggregates. In this project, we plan to design and synthesize BODIPY-based near-infrared dual-functional fluorescent probes with two structural characteristics, rotatable double bond at the meso site (response towards microenvironments) and D-π-A (easily combined with Aβ aggregates), which can reduce the flexibility of the molecule and prevent the free rotation of the meso site in the presence of lysosomal viscosity increase and Aβ aggregates, and therefore realize the dual detection in solutions and biological systems through different extent of “fluorescence enhancements”and “wavelength red-shifts”. By optimizing the molecular structure and clarifying its structure-activity relationship, we aim to develop novel near-infrared dual-functional fluorescent probes those can detect lysosomal viscosity and Aβ aggregates simultaneously, and thus provide new ideas and methods for the AD’s pathogenesis research.