Choroid plexus-derived extracellular vesicles exhibit brain targeting characteristics

Marie J Pauwels; Junhua Xie; Adam Ceroi; Sriram Balusu; Jonas Castelein; Elien Van Wonterghem; Griet Van Imschoot; Andrew Ward; Trevelyan R Menheniott; Oskar Gustafsson; Francis Combes; Samir El Andaloussi; Niek N Sanders; Imre Mäger; Lien Van Hoecke; Roosmarijn E Vandenbroucke

doi:10.1016/j.biomaterials.2022.121830

Choroid plexus-derived extracellular vesicles exhibit brain targeting characteristics

Biomaterials. 2022 Nov:290:121830. doi: 10.1016/j.biomaterials.2022.121830. Epub 2022 Oct 6.

Authors

Marie J Pauwels¹, Junhua Xie¹, Adam Ceroi¹, Sriram Balusu², Jonas Castelein¹, Elien Van Wonterghem¹, Griet Van Imschoot¹, Andrew Ward³, Trevelyan R Menheniott⁴, Oskar Gustafsson⁵, Francis Combes⁶, Samir El Andaloussi⁵, Niek N Sanders⁷, Imre Mäger⁸, Lien Van Hoecke¹, Roosmarijn E Vandenbroucke⁹

Affiliations

¹ VIB Center for Inflammation Research, VIB, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.
² VIB Center for the Biology of Disease, VIB, Herestraat 49, 3000, Leuven, Belgium.
³ Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
⁴ Murdoch Children's Research Institute, Flemington Rd. Parkville, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Flemington Rd. Parkville, Melbourne, Victoria, Australia.
⁵ Department of Laboratory Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
⁶ Department of Biotechnology and Nanomedicine, SINTEF AS, Sem Sælands V. 2A, N-7034 Trondheim, Norway.
⁷ Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium; Cancer Research Institute Ghent (CRIG), 9000, Ghent, Belgium.
⁸ Institute of Technology, University of Tartu, 50 411, Tartu, Estonia; Department of Paediatrics, University of Oxford, Oxford, OX3 9DU, UK.
⁹ VIB Center for Inflammation Research, VIB, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium. Electronic address: roosmarijn.vandenbroucke@irc.vib-ugent.be.

PMID: 36302306
DOI: 10.1016/j.biomaterials.2022.121830

Abstract

The brain is protected against invading organisms and other unwanted substances by tightly regulated barriers. However, these central nervous system (CNS) barriers impede the delivery of drugs into the brain via the blood circulation and are therefore considered major hurdles in the treatment of neurological disorders. Consequently, there is a high need for efficient delivery systems that are able to cross these strict barriers. While most research focuses on the blood-brain barrier (BBB), the design of drug delivery platforms that are able to cross the blood-cerebrospinal fluid (CSF) barrier, formed by a single layer of choroid plexus epithelial cells, remains a largely unexplored domain. The discovery that extracellular vesicles (EVs) make up a natural mechanism for information transfer between cells and across cell layers, has stimulated interest in their potential use as drug delivery platform. Here, we report that choroid plexus epithelial cell-derived EVs exhibit the capacity to home to the brain after peripheral administration. Moreover, these vesicles are able to functionally deliver cargo into the brain. Our findings underline the therapeutic potential of choroid plexus-derived EVs as a brain drug delivery vehicle via targeting of the blood-CSF interface.

Keywords: Blood-cerebrospinal fluid (CSF) barrier; Brain barriers; Brain delivery; Extracellular vesicles (EVs).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood-Brain Barrier / physiology
Brain
Central Nervous System
Choroid Plexus*
Extracellular Vesicles*

Abstract

Publication types

MeSH terms

Grants and funding