Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430071, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Angew Chem Int Ed Engl. 2023 Nov 13;62(46):e202313137. doi: 10.1002/anie.202313137. Epub 2023 Oct 13.
To realize sensing and labeling biomarkers is quite challenging in terms of designing multimodal imaging probes. In this study, we developed a novel β-galactosidase (β-gal) activated bimodal imaging probe that combines near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) to enable real-time visualization of activity in living organisms. Upon β-gal activation, Gal-Cy-Gd-1 exhibits a remarkable 42-fold increase in NIR fluorescence intensity at 717 nm, allowing covalent labeling of adjacent target enzymes or proteins and avoiding molecular escape to promote probe accumulation at the tumor site. This fluorescence reaction enhances the longitudinal relaxivity by approximately 1.9 times, facilitating high-resolution MRI. The unique features of Gal-Cy-Gd-1 enable real-time and precise visualization of β-gal activity in live tumor cells and mice. The probe's utilization aids in identifying in situ ovarian tumors, offering valuable assistance in the precise removal of tumor tissue during surgical procedures in mice. The fusion of NIR fluorescence and MRI activation through self-immobilizing target enzymes or proteins provides a robust approach for visualizing β-gal activity. Moreover, this approach sets the groundwork for developing other activatable bimodal probes, allowing real-time in vivo imaging of enzyme activity and localization.
在设计多模态成像探针方面，实现对生物标志物的传感和标记极具挑战性。在本研究中，我们开发了一种新型的β-半乳糖苷酶（β-gal）激活的双模态成像探针，它结合了近红外（NIR）荧光和磁共振成像（MRI），以实现对活生物体中活性的实时可视化。在β-gal 激活后，Gal-Cy-Gd-1 在 717nm 处的近红外荧光强度显著增加了 42 倍，允许对相邻的靶酶或蛋白质进行共价标记，并避免分子逃逸，以促进探针在肿瘤部位的积累。这种荧光反应使纵向弛豫率提高了约 1.9 倍，有利于高分辨率 MRI。Gal-Cy-Gd-1 的独特特性使我们能够实时、精确地可视化活肿瘤细胞和小鼠中的β-gal 活性。该探针的应用有助于识别原位卵巢肿瘤，为在小鼠手术过程中精确切除肿瘤组织提供了有价值的帮助。通过自固定靶酶或蛋白质实现 NIR 荧光和 MRI 激活的融合，为可视化β-gal 活性提供了一种强大的方法。此外，这种方法为开发其他可激活的双模态探针奠定了基础，使我们能够实时进行体内成像以观察酶活性和定位。
