Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Mass Spectrum Center, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Sci Rep. 2024 Jan 16;14(1):1336. doi: 10.1038/s41598-023-50789-8.
Early diagnosis and intervention of Alzheimer's disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood-brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 μm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.
阿尔茨海默病（AD）的早期诊断和干预对延缓病理进展尤为重要。尽管荧光探针已被广泛用于 AD 的研究和诊断，但由于其在体内血脑屏障（BBB）的穿透能力较低，其生物应用受到了显著限制。在本研究中，我们报告了第一个靶向高尔基体的双光子（TP）荧光探针 DCM-DH，用于检测高尔基体中的粘度。该探针经过合理设计，具有出色的分析性能，包括高灵敏度、特异的高尔基体靶向、高效的 BBB 穿透能力和在 AD 模型小鼠大脑中的深组织穿透能力（247μm）。使用该探针，我们证明了人肝癌细胞（HepG2 细胞）中的荧光强度高于人正常肝细胞（LO2 细胞），并且 AD 模型小鼠的大脑粘度显著增加。我们预计，这种有能力的工具可以很容易地扩展到其他 AD 生物标志物，用于对这种有害疾病的基础研究。
