An Iodinated BODIPY-Based Probe for the Selective Mapping and Disassembly of Amyloid-β Aggregates In Vivo

Neurotoxic amyloid-β (Aβ) aggregates are recognized as a central pathogenic factor in Alzheimer's disease (AD). Targeted photooxygenation offers an effective approach to promoting their degradation. Herein, we developed an iodinated BODIPY-based probe (BocIBDP) for the selective mapping (<i>K</i>_d = 125.9 nM, signal-to-noise ratio (S/N) = 4.1) and photooxygenation of Aβ aggregates. The introduction of iodine atoms endows BocIBDP with an efficient reactive oxygen species (ROS) generation capacity through enhanced intersystem crossing. Remarkably, Aβ binding enhanced the probe's ability to generate ROS, thereby facilitating photodynamic oxidation of Aβ aggregates. In vivo assays showed that BocIBDP can selectively stain Aβ plaques and reduce Aβ deposition in the brains of APP/PS1 mice, alleviating symptoms of cognitive impairment and memory loss. These studies highlight the potential of BocIBDP as a dual-function probe for early diagnosis and therapeutic intervention in AD.