Chalcogenapyrylium-engineered D-π-A probe for enhanced optoacoustic imaging of amyloid-β plaques

High-resolution optoacoustic visualization of amyloid-β (Aβ) plaques facilitates assessment of Alzheimer's disease (AD)’s states and related pathological mechanisms. However, it still lacks effective Aβ-probes due to suboptimal optoacoustic properties. In this study, we proposed the use of N, N-dimethylaniline as the Aβ recognition unit and chalcogenapyrylium as the acceptor to construct a novel D-π-A typed probe (DMA-Te). This design not only enhances the near-infrared optoacoustic signal but also maintains this enhancement upon Aβ fibrils binding through the preservation of twisted intramolecular charge transfer state. Furthermore, the stringent structure of DMA-Te exhibits high blood-brain barrier permeability and Aβ-binding capacity. Leveraging these advantages, dual-wavelength optoacoustic microscopy can effectively visualize Aβ plaques and diminished blood vessels in the AD brain. Therefore, this study presents a promising optoacoustic probe for the detailed depiction of AD progression.