Ampholytic Carbon Dots Enable Imaging and Modulation of Amyloid Fibrillation with Reduced Neurotoxicity

Abstract

Neurodegenerative diseases like Alzheimer’s are driven by protein aggregation, notably amyloid-β (Aβ) fibrillation and associated cytotoxicity. Here, we report the design of ampholytic carbon dots (ACDs) with red/green emission that bind/control amyloid fibrillation. These ACDs bind with amyloid structures via electrostatic and van der Waals interactions and effectively inhibit fibril formation as well as promote disintegration of mature fibrils. The fluorescence property of ACDs enable high-resolution fluorescence imaging of amyloid structures at intra/extracellular space. ACD–amyloid conjugates showed lysosomal entrapment with lower amyloid-induced cytotoxicity via the lowering of reactive oxygen species generation. Together, these results highlight the dual functionality of ACDs as imaging and antiamyloidogenic agents, offering a promising nanoplatform for the diagnosis and treatment of amyloid-associated neurodegenerative disorders.