Ultrasonic disruption of circulating amyloid β aggregates via phase-change peptide nanoemulsions

Abstract

Amyloid β (Aβ) assemblies exist not only in the central nervous system, but can circulate within the bloodstream to trigger and exacerbate peripheral, cerebrovascular, and neurodegenerative disorders. Eliminating excess peripheral Aβ fibrils, therefore, holds promise to improve the management of amyloid-related diseases. Here, we present nanoemulsion-mediated ultrasonic ablation of circulating Aβ fibrils to both destroy established plaques and prevent the re-growth of ablated fragments back into toxic species. This approach is made possible using a de novo designed peptide emulsifier that contains the self-associating sequence from the amyloid precursor protein. Emulsification of the peptide surfactant with fluorous nanodroplets produces contrast agents that rapidly adsorb Aβ assemblies and allows their ultrasound-controlled destruction via acoustic cavitation. Vessel-mimetic flow experiments demonstrate that nanoemulsion-assisted Aβ disruption can be achieved in circulation using clinical diagnostic ultrasound transducers. Additional cell-based assays confirm the ablated fragments are less toxic to neuronal and glial cells compared to mature fibrils, and can be rapidly phagocytosed by both peripheral and brain macrophages. These results highlight the potential of nanoemulsion contrast agents to deliver new imaging enabled strategies for non-invasive management of Aβ-related diseases using traditional diagnostic ultrasound modalities.