Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease.
Parkinson's disease
brain targeting
central nervous system
lipid nanoparticles
neuroinflammation
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
27 Sep 2023
27 Sep 2023
Historique:
revised:
04
09
2023
received:
17
05
2023
pubmed:
27
9
2023
medline:
27
9
2023
entrez:
27
9
2023
Statut:
aheadofprint
Résumé
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, it is demonstrated 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 are decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100-nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve 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.
Identifiants
pubmed: 37753928
doi: 10.1002/adma.202304654
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2304654Subventions
Organisme : European Research Council
ID : 101089009
Pays : International
Informations de copyright
© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.
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