Enhanced β-Amyloid Aggregation in Living Cells Imaged with Quinolinium-Based Spontaneous Blinking Fluorophores

Abnormal accumulation of intracellular and extracellular β-amyloid (Aβ) aggregates is closely related to the pathogenesis of Alzheimer's disease (AD). In this work, we use quinolinium derivatives with electron-rich aniline substituents as the skeletons to develop a set of spontaneous blinking fluorophores by the formation of long-lived radicals. These probes can target Aβ_1-40 aggregates and exhibit strong deep-red emission upon binding to Aβ_1-40 aggregates. More importantly, at the single-molecule level, these probes display spontaneous blinking, low duty cycle, and high photon output, which are suitable for the nanoscopic imaging of Aβ aggregates in living cells. The assembly process of the Aβ aggregates was then tracked with nanoscopic imaging. The elongation rate on the cell membrane was noticeably fast over that in the solution. This work provides a feasible strategy for the design of spontaneous blinking fluorophores for Aβ aggregates.