β-半乳糖苷酶激活的近红外II区分子探针用于乳腺癌的早期诊断研究

NIR-II fluorescent probes have been widely used in biochemistry, materials science, clinical medicine and other fields owning to the advantages of high resolution and deep-tissue penetration. In particular, developing intelligent fluorescent probes for targeting biomarkers and determining their distribution and concentration in biological systems benefits to revealing the physiological and pathological functions of biomolecules, which provides a new strategy for the prevention, diagnosis and treatment of diseases. In this project, an activable NIR-II fluorescent probe β-Mir-BOD with good photostability was designed and developed. β-galactose was introduced into the parent nucleus of mirror BODIPY by molecular engineering design strategy to identify β-galactosidase. When β-galactose were hydrolysis by the glycosidic bond of β-galactosidase, it will be generated monosaccharide and β-Mir-BOD-O-, which forms the rational fluorescence in the NIR-II window, this change can self-calibrate with the fluorescent signal of β-Mir-BOD and the new fluorescence signal after responding to enzyme, so the background disturbance is lesser, which can more accurately realize the quantitative detection. Finally, NIR-II fluorescence imaging was used to realize the early diagnosis of breast cancer accurately.

近红外二区（NIR-II）荧光探针因组织穿透能力深和高分辨率的优点在生物化学、材料科学以及临床医学等领域得到广泛应用。发展以生物标志物为靶点的智能型荧光探针，确定这些标志物在生物体系中的分布及浓度，有利于揭示生物分子相关的生理及病理功能，为疾病的预防、诊断和治疗提供新思路。本项目设计开发了一种光稳定性好的可激活型NIR-II有机探针β-Mir-BOD。通过分子工程设计策略在镜像BODIPY母核结构上引入β-半乳糖用于识别β-半乳糖苷酶。当探针分子内的β-半乳糖被β-半乳糖酶的水解糖苷键水解为单糖后会生成Mir-BOD-O-，荧光信号在NIR-II窗口产生比率式变化，这种变化利用探针β-Mir-BOD自身荧光信号以及与酶响应后产生的新荧光信号进行自校准，受到的背景干扰较小，可以更精准地实现定量检测。最后利用NIR-II荧光成像技术优势精准实现对乳腺癌的早期诊断。

肿瘤的致死率之所以高主要是由于其发现多处于中晚期导致的，因此针对肿瘤早筛的问题做研究具有重大的生命意义。近红外二区（NIR-II）荧光探针因组织穿透能力深和高分辨率的优点在生物化学、材料科学以及临床医学等领域得到广泛应用。发展以生物标志物为靶点的智能型荧光探针，确定这些标志物在生物体系中的分布及浓度，有利于揭示生物分子相关的生理及病理功能，为疾病的预防、诊断和治疗提供新思路。本项目开发了一种酶响应探针Mir-BOD。首先通过分子工程设计策略在镜像BODIPY母核结构上引入β-半乳糖用于识别β-半乳糖苷酶。探针合成相对容易，成功得到分子后探究了其光学性能，发现探针具有很好的稳定性，不易光漂白，且水溶性好；荧光量子产率高且摩尔消光系数大，通过动物成像系统发现是一种很好的近红外二区成像探针，在生物成像方面有一定的应用前景。