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.