Polarity-responsive fluorescence lifetime probe for in vivo imaging of Aβ plaque dynamics: Unveiling PBM-induced Aβ polarity reversal
Zhenlong Huang, Yiqiang Wang, Fangrui Lin, Ziyi Luo, Hao Xu, Nuernisha Alifu, Jia Li, Xiaoyu Weng, Yiwen Sun, Jun Song, Liwei Liu, Yu Chen, Junle Qu
Abstract
Photobiomodulation (PBM) has gained significant attention as a potential therapy for Alzheimer disease (AD) due to its role in promoting amyloid-β (Aβ) plaque clearance. However, its effects on the physicochemical properties of Aβ plaques before clearance remain poorly understood. Here, we introduce SiR-Aβ, a novel polarity-sensitive fluorescence lifetime probe with high blood-brain barrier permeability and selective Aβ plaque binding, enabling dynamic in vivo monitoring of plaque polarity. SiR-Aβ exhibits high sensitivity to environmental polarity, with its fluorescence lifetime increasing as polarity decreases. Fluorescence lifetime imaging (FLIM) revealed a gradual lifetime increase during plaque development, indicating reduced polarity. Notably, 40 Hz visible light stimulation induced a PBM-driven reversal of Aβ plaque polarity, independent of plaque size and preceding plaque clearance. These findings provide new insights into PBM's mechanism in targeting Aβ plaques and suggest polarity changes as a potential early marker for assessing PBM treatment efficacy.