Rational design of molecular rotor-based fluorescent probes with bi-aromatic rings for efficient in vivo detection of amyloid-β plaques in Alzheimer's disease

The presence of A beta plaques in the brain is a hallmark of Alzheimer's disease. Here, we designed and synthesized a series of molecular rotors with various bi-aromatic rings and investigated their applications as near-infrared (NIR) probes for A beta plaques. We found that the interaction with A beta aggregates hindered the rotational freedom of the molecular rotors, which brought about a noticeable enhancement in fluorescence intensity. Among them, probe 4b (K-d = 8.5 nM) with a phenyl-pyridine ring showed a 98-fold increase in fluorescence intensity upon binding with A beta aggregates. In addition, 4b could identify A beta plaques in brain sections of both a transgenic (Tg) mouse and AD patients. Furthermore, 4b could readily penetrate the mouse blood-brain barrier (brain(2min) = 10.11% ID/g) and washed out rapidly. Finally, the NIR imaging with Tg mice confirmed the practical application of 4b in detecting A beta plaques in vivo. Altogether, our work widens the landscape of A beta NIR probes and offers a new tool for A beta detection.

Automated summary

In this study, a series of molecular rotors were designed and synthesized as near-infrared probes for detecting A beta plaques. The interaction with A beta aggregates significantly enhanced the fluorescence intensity of the molecular rotors. Among them, probe 4b showed a 98-fold increase in fluorescence intensity upon binding with A beta aggregates and was able to identify A beta plaques in brain sections of both transgenic mice and AD patients.