期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 16, 页码 18525-18532出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c01585
关键词
gadolinium(III) complex-cyanine; multimodal contrast agent; amyloid-beta targeting; in vivo MR imaging
资金
- General Research Fund of Research Grants Council of Hong Kong [HKBU12302620]
- National Natural Science Foundation of China [21675135, 21974119]
- Interdisciplinary Research Clusters Matching Scheme [IRCMS-19-20H02A]
- Research Committee of Hong Kong Baptist University
- Hunan Provincial Natural Science Foundation of China [2019JJ30020]
- Conseil Regional de Bourgogne Franche Comte
- European Union through the PO FEDER-FSE Bourgogne 2014/2020 programs
The developed Gd(DOTA)-cyanine dyad is the first imaging probe targeting Aβ that can be applied for one- and two-photon excited fluorescence and magnetic resonance imaging in AD mouse models. It possesses various desirable properties such as good biocompatibility, high Aβ selectivity, strong fluorescence enhancement, and inhibition of Aβ aggregation and toxicity. This theranostic probe shows promise for diagnosis and therapy of AD and has potential for MRI imaging of Aβ in humans.
Despite the wide use of magnetic resonance imaging (MRI) as a clinical diagnostic tool, there are still no clinically approved MRI contrast agents that can be applied for cerebral Alzheimer's disease (AD) biomarker imaging. We report here the design and development of the first amyloid-beta (A beta)-targeted, blood-brain barrier (BBB) penetrable theranostic Gd(DOTA)-cyanine dyad, which was synthesized by the conjugation of Gd(DOTA) complex and carbazole-based cyanine dye by the copper(I)-catalyzed azide-alkyne cycloaddition click reaction for imaging of A beta in vivo and ex vivo in AD mouse models. This dyad, as a multimodal probe, possesses desirable multifunctional properties, including good biocompatibility, low cytotoxicity, high A beta selectivity, strong fluorescence enhancement upon binding with A beta species, good paramagnetic properties, high stability, good BBB penetrability, and fast elimination from the mouse. The longitudinal relaxivity (r(1)) of the dyad was found to be 4.42 mM(-1) s(-1) at 3 T, suggesting it to be promising as a T-1-weighted MRI contrast agent. The probe has been successfully demonstrated to be able to be applied for one- and two-photon excited fluorescence and magnetic resonance (MR) imaging of A beta in transgenic mouse models of AD. In addition, it can inhibit A beta aggregation, protect against toxicity induced by A beta, and suppress A beta-induced reactive oxygen species (ROS) production. Our results demonstrate the highly promising theranostic capability of the dyad for diagnosis and therapy of AD and extraordinary potential for MRI of A beta in humans.
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