A Ratiometric Fluorescent Conjugated Oligomer for Amyloid β Recognition, Aggregation Inhibition, and Detoxification

The sensitive recognition and effective inhibition of toxic amyloid β protein (Aβ) aggregates play a critical role in early diagnosis and treatment of neurodegenerative diseases. In this work, a new conjugated oligo(fluorene-co-phenylene) (OFP) modified with 1,8-naphthalimide (NA) derivative OFP-NA-NO₂ is designed and synthesized as a ratiometric fluorescence probe for sensing Aβ, inhibiting the assembly of Aβ, and detoxicating the cytotoxicity of Aβ aggregates. In the presence of Aβ, the active ester group on the side chain of OFP-NA-NO₂ can covalently react with the amino group on Aβ, effectively inhibiting the formation of Aβ aggregates and degrading the preformed fibrils. In this case, the fluorescence intensity ratio of NA to OFP (I_NA /I_OFP ) increases greatly. The detection limit is calculated to be 89.9 nM, presenting the most sensitive ratiometric recognition of Aβ. Interestingly, OFP-NA-NO₂ can dramatically recover the cell viability of PC-12 and restore the Aβ-clearing ability of microglia. Therefore, this ratiometric probe exhibits the targeted recognition of Aβ, effective inhibition of Aβ aggregates, and detox effect, which is potential for early diagnosis and treatment of neurodegenerative diseases.