Biodegradable Poly(trehalose) Nanoparticle for Preventing Amyloid Beta Aggregation and Related Neurotoxicity

Trehalose is a disaccharide that is capable of inhibiting protein aggregation and activating cellular autophagy. It has been shown that a polymer or nanoparticle form, terminated with multiple trehalose units, can significantly enhance the anti-amyloidogenic performance and is suitable for the treatment of neurodegenerative diseases. Here, we report a trehalose-conjugated polycarbonate-co-lactide polymer and formulation of its nanoparticles having multiple numbers of trehalose exposed on the surface. The resultant poly­(trehalose) nanoparticle inhibits the aggregation of amyloid beta peptides and disintegrates matured amyloid fibrils into smaller fragments. Moreover, the poly­(trehalose) nanoparticle lowers extracellular amyloid β oligomer-driven cellular stress and enhances cell viability. The presence of biodegradable polycarbonate components in the poly­(trehalose) nanoparticle would enhance their application potential as an anti-amyloidogenic material.