Monoclonal antibodies (mAbs) hold promise in treating Parkinson’s disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, we demonstrate that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby allowing 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. 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. Within neurons, SynO4 was released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In-vivo , intravenous BTL administration resulted in a 7-fold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improved behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.
【저자키워드】 Lipid nanoparticles, Neuroinflammation, Parkinson’s disease, brain targeting, central nervous system.,