A theranostic agent for in vivo near-infrared imaging of β-amyloid species and inhibition of β-amyloid aggregation

Amyloid-β (Aβ) peptide as one of the main components of senile plaques is closely related to the onset and progression of incurable Alzheimer's disease (AD). Numerous efforts have been devoted to develop probes for Aβ species/plaque imaging for AD diagnostics and to develop aggregation inhibitors preventing formation of toxic soluble oligomeric Aβ for therapeutics. Herein, for the first time, a series of novel charged molecules, which can simultaneously perform near infra-red in vivo imaging of Aβ species/plaques in animal model and inhibition of self-aggregation of Aβ monomer from forming toxic oligomers, are reported. Among them, DBA-SLOH showed excellent blood-brain barrier (BBB) permeability and biocompatibility due to the incorporation of lipophilic alkyl chains with moderate length into the charged skeleton. Importantly, DBA-SLOH was found to have a high binding affinity toward Aβ species exhibiting a dramatic fluorescence enhancement upon interacting with Aβ species. Despite a weaker binding with Aβ monomers as compared to Aβ aggregates, DBA-SLOH could effectively prevent the Aβ_1-40 and Aβ_1-42 peptides from self-aggregation and forming toxic oligomers. This multifunctional fluorescent molecule shows promising potential as a theranostic agent for the diagnosis and therapy of AD.