Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms of Parkinson's Disease.

Monoclonal antibodies (mAbs) hold promise for treating Parkinson's disease (PD), but their therapeutic use is hindered by poor delivery to the brain. In this study, we demonstrate that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby improving the intracellular and extracellular treatment of the PD brain. BTL were decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. The BTL were loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD. We show that 100-nm BTL cross human BBB models intact and were taken up by primary neurons. Inside the neurons, SynO4 is released from the nanoparticles and binds to its target, thereby reducing AS aggregation and increasing neuronal viability. In-vivo, intravenous administration of BTL led to a 7-fold increase of mAbs in brain cells, reducing AS aggregation and neuroinflammation. In addition, BTL treatments improved behavioral motor function and learning ability in mice, with a favorable safety profile. Targeted nanotechnologies are promising platforms for delivering medicines to treat brain neurodegeneration. This article is protected by copyright. All rights reserved.