Development of novel near-infrared GFP chromophore-based fluorescent probes for imaging of amyloid-β plaque and viscosity

Alzheimer's disease (AD) is closely associated with abnormal deposition of amyloid β (Aβ) peptides and formation of plaques. Green fluorescent protein (GFP) chromophores with a high-quality biomimetic fluorophore skeleton, have been extensively explored in biomedical diagnosis. However, its applications in intact animals were highly limited due to their short excitations and emissions owing to the absorption, scattering and auto-fluorescence by endogenous substances. In this work, through π-extension of the double bond bridge between the aromatic and imidazolidinone rings of the GFP chromophore, the emission of CX1 reached NIR window (over 702 nm) and what’s more interesting, the affinity of CX1 with Aβ aggregates was obviously improved. CX1 effectively avoided the limit in vivo imaging due to short excitation and emission and showed higher selectivity and signal-to-noise ratio towards Aβ plaques. In the hydrophobic cavity of Aβ aggregates or increased viscosity, the free rotation of CX1 was efficiently limited due to inhibition of twisted intramolecular charge transfer and thus the fluorescence emission exhibited a significant increase. Furthermore, CX1 can clearly image Aβ aggregates in the brain of transgenic mice and viscosity in living cells, which could serve as an effective tool for monitoring the pathological process of AD.