Near-Infrared Room-Temperature Phosphorescent Organic Nanoparticles for Amyloid-β Targeting and Time-Resolved Imaging

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which the amyloid-beta (Aβ) deposit is widely recognized as a defining hallmark. Therefore, the development of robust probes capable of monitoring the aberrant aggregation and fibrillization of central Aβ aggregates is of paramount importance. However, conventional fluorescence-based assays for Aβ aggregates imaging are hampered by background interference and low specificity. Herein, we report a facile approach for the construction of organic room-temperature phosphorescence (RTP) nanoparticles through a host-guest doping strategy. The rationally engineered nanoparticles exhibit near-infrared emission (650-800 nm) and a prolonged phosphorescence lifetime (109 μs) and demonstrate exceptional blood-brain barrier permeability coupled with precise targeting of Aβ aggregates. Their unique optical and biological properties enable highly sensitive and time-resolved imaging of Aβ deposits, effectively enhancing the signal-to-noise ratios. Furthermore, the nanoparticles inhibit Aβ fibrillization and mitigate associated neurotoxicity in vitro, underscoring their theranostic potential for AD.