Recently, Angew. Chem. Int. Ed.,the top international academic journal, published online a research paper by the team led by Prof. Liang Gaolin from the School of Biological Sciences & Medical Engineering/State Key Laboratory of Digital Medical Engineering at Southeast University, titled “A 19F MRI/NIR-FL Nanoprobe for ‘Turn-On’ Imaging of β-Secretase (BACE1) Activity in Alzheimer’s Disease.” This study successfully developed a β-secretase (BACE1)-activatable nanoprobe that undergoes in situ disassembly upon specific cleavage by BACE1, thereby “turning on” 19F magnetic resonance imaging/near-infrared fluorescence (19F MRI/NIR-FL) signals for highly sensitive imaging analysis of Alzheimer’s disease (AD) (Angew. Chem. Int. Ed. 2026, DOI:10.1002/anie.1325073).
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that has become a major burden on global public health systems. Currently, there are no effective treatments to halt or reverse the disease, making early diagnosis of AD crucial for timely intervention and delaying disease progression. β-Secretase (BACE1) is a highly promising biomarker for the early stages of AD; however, methods for its in vivo imaging have rarely been reported. To address this, Prof. Liang Gaolin’s team designed a BACE1-activatable nanoprobe, 19F-Cy5.5-NP, for 19F MRI/NIR-FL imaging of AD in living organisms. As shown in the above Fig. a, the authors rationally designed a precursor molecule, Cys(StBu)-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe(CF?)-Lys(Cy5.5)-CBT (19F-Cy5.5), which contains four functional moieties: (1) StBu-protected cysteine (Cys) at one end and a 6-amino-2-cyanobenzothiazole (CBT) group at the other end, for reduction-triggered CBT-Cys click reaction; (2) an octapeptide sequence Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe, serving as the BACE1 cleavage substrate; (3) a CF? group as the 19F signal source; and (4) a Cy5.5 fluorophore for near-infrared fluorescence imaging. Upon reduction-triggered CBT-Cys click reaction in vitro, 19F-Cy5.5 forms a cyclic dimer (19F-Cy5.5-Dimer), which further self-assembles into nanoparticles (19F-Cy5.5-NP). Nanoparticle formation induces rapid transverse relaxation of 19F nuclear spins and an “intra-/inter-molecular dual quenching” effect of the fluorophore, thereby keeping the 19F MRI/NIR-FL signals of the nanoprobe in an “off” state. The mechanism of action of the nanoprobe is illustrated in the above Fig. b. When the nanoprobe reaches AD lesions, it is specifically cleaved by BACE1, causing disassembly of 19F-Cy5.5-NP and simultaneous “turn-on” of both 19F MR and NIR-FL signals. The “turned-on” 19F MR signal enables highly specific imaging of BACE1 activity, while the NIR-FL signal provides high-spatial-resolution secondary confirmation. Cell experiments demonstrated that the 19F MRI/NIR-FL signals generated by 19F-Cy5.5-NP in Aβ?????-treated PC12 cells were 4.6-fold and 1.5-fold higher, respectively, than those in normal PC12 cells. Furthermore, this “turn-on” 19F MRI/NIR-FL strategy enabled precise imaging of BACE1 in an AD zebrafish model, opening up new avenues for early detection of AD.
Xu Lingling, a recent Ph.D. graduate from the School of Biological Sciences and Medical Engineering, and Jiang Qiaochu, a current Ph.D. student, are the co-first authors of the paper. Prof. Liang Gaolin, serving as Chair Professor at Southeast University and Deputy Director of the State Key Laboratory of Digital Medical Engineering, is the lead corresponding author. Associate Prof. Zhan Wenjun of Southeast University and Prof. Yang Zhanjun of Yangzhou University are co-corresponding authors. This work was supported by the National Key Research and Development Program of China, the Key Program of the National Natural Science Foundation of China, the Jiangsu Provincial Key Research and Development Program (Frontier Leading Technology Basic Research Major Project), the Jiangsu Provincial Innovation and Entrepreneurship Team Program, and the Southeast UniversityZhishan Young Scholars Program, among others.
Paper’s link: https://onlinelibrary.wiley.com/doi/10.1002/anie.1325073
Source: School of Biological Sciences & Medical Engineering, 91抖淫
Translated by: Melody Zhang
Edited by: Leah Li
